Inflammation, Autoimmunity and Neurodegenerative Diseases, Therapeutics and Beyond
Language English Country United Arab Emirates Media print
Document type Journal Article
Grant support
23-06301J
Grant Agency of the Czech Republic
LX22NPO5102
National Institute for Cancer Research
LX22NPO5107
National Institute for Neurological Research
LX22NPO5103
National Institute of virology and bacteriology
TN02000109
European Union - Next Generation EU from the Ministry of Education, Youth and Sports of the Czech Republic (MEYS)
PubMed
37898823
PubMed Central
PMC10964103
DOI
10.2174/1570159x22666231017141636
PII: CN-EPUB-135280
Knihovny.cz E-resources
- Keywords
- Alzheimer's disease (AD), Neurodegenerative diseases (NDs), Parkinson's disease (PD), autoimmunity, neurodegeneration, neuroinflammation, tau, therapy, vaccines., α-synuclein, β-amyloid,
- MeSH
- alpha-Synuclein MeSH
- Alzheimer Disease * drug therapy MeSH
- Autoimmunity MeSH
- Autoimmune Diseases * MeSH
- Cytokines MeSH
- Humans MeSH
- Neurodegenerative Diseases * therapy MeSH
- Parkinson Disease * drug therapy MeSH
- Inflammation MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- alpha-Synuclein MeSH
- Cytokines MeSH
Neurodegenerative disease (ND) incidence has recently increased due to improved life expectancy. Alzheimer's (AD) or Parkinson's disease (PD) are the most prevalent NDs. Both diseases are poly genetic, multifactorial and heterogenous. Preventive medicine, a healthy diet, exercise, and controlling comorbidities may delay the onset. After the diseases are diagnosed, therapy is needed to slow progression. Recent studies show that local, peripheral and age-related inflammation accelerates NDs' onset and progression. Patients with autoimmune disorders like inflammatory bowel disease (IBD) could be at higher risk of developing AD or PD. However, no increase in ND incidence has been reported if the patients are adequately diagnosed and treated. Autoantibodies against abnormal tau, β amyloid and α- synuclein have been encountered in AD and PD and may be protective. This discovery led to the proposal of immune-based therapies for AD and PD involving monoclonal antibodies, immunization/ vaccines, pro-inflammatory cytokine inhibition and anti-inflammatory cytokine addition. All the different approaches have been analysed here. Future perspectives on new therapeutic strategies for both disorders are concisely examined.
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Price D.L., Sisodia S.S., Borchelt D.R. Genetic neurodegenerative diseases: the human illness and transgenic models. Science. 1998;282(5391):1079–1083. doi: 10.1126/science.282.5391.1079. PubMed DOI
MacDonald M. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. Cell. 1993;72(6):971–983. doi: 10.1016/0092-8674(93)90585-E. PubMed DOI
Akçimen F., Lopez E.R., Landers J.E., Nath A., Chiò A., Chia R., Traynor B.J. Amyotrophic lateral sclerosis: Translating genetic discoveries into therapies. Nat. Rev. Genet. 2023;24(9):642–658. doi: 10.1038/s41576-023-00592-y. PubMed DOI PMC
Papiri G., D’Andreamatteo G., Cacchiò G., Alia S., Silvestrini M., Paci C., Luzzi S., Vignini A. Multiple sclerosis: Inflammatory and neuroglial aspects. Curr. Issues Mol. Biol. 2023;45(2):1443–1470. doi: 10.3390/cimb45020094. PubMed DOI PMC
Klotz L., Antel J., Kuhlmann T. Inflammation in multiple sclerosis: Consequences for remyelination and disease progression. Nat. Rev. Neurol. 2023;19(5):305–320. doi: 10.1038/s41582-023-00801-6. PubMed DOI
Balcerac A., Louapre C. Genetics and familial distribution of multiple sclerosis: A review. Rev. Neurol. 2022;178(6):512–520. doi: 10.1016/j.neurol.2021.11.009. PubMed DOI
Breijyeh Z., Karaman R. Comprehensive review on Alzheimer’s disease: Causes and treatment. Molecules. 2020;25(24):5789. doi: 10.3390/molecules25245789. PubMed DOI PMC
Rizek P., Kumar N., Jog M.S. An update on the diagnosis and treatment of Parkinson disease. CMAJ. 2016;188(16):1157–1165. doi: 10.1503/cmaj.151179. PubMed DOI PMC
Aborode A.T., Pustake M., Awuah W.A., Alwerdani M., Shah P., Yarlagadda R., Ahmad S., Silva C.I.F., Chandra A., Nansubuga E.P., Abdul-Rahman T., Mehta A., Ali O., Amaka S.O., Zuñiga Y.M.H., Shkodina A.D., Inya O.C., Shen B., Alexiou A. Targeting oxidative stress mechanisms to treat Alzheimer’s and Parkinson’s disease: A critical review. Oxid. Med. Cell. Longev. 2022;2022:1–9. doi: 10.1155/2022/7934442. PubMed DOI PMC
Gorlé N., Van Cauwenberghe C., Libert C., Vandenbroucke R.E. The effect of aging on brain barriers and the consequences for Alzheimer’s disease development. Mamm. Genome. 2016;27(7-8):407–420. doi: 10.1007/s00335-016-9637-8. PubMed DOI
Dai M.H., Zheng H., Zeng L.D., Zhang Y. The genes associated with early-onset Alzheimer’s disease. Oncotarget. 2018;9(19):15132–15143. doi: 10.18632/oncotarget.23738. PubMed DOI PMC
Sumirtanurdin R., Thalib A.Y., Cantona K., Abdulah R. Effect of genetic polymorphisms on Alzheimer’s disease treatment outcomes: An update. Clin. Interv. Aging. 2019;14:631–642. doi: 10.2147/CIA.S200109. PubMed DOI PMC
Sarnowski C., Ghanbari M., Bis J.C., Logue M., Fornage M., Mishra A., Ahmad S., Beiser A.S., Boerwinkle E., Bouteloup V., Chouraki V., Cupples L.A., Damotte V., DeCarli C.S., DeStefano A.L., Djoussé L., Fohner A.E., Franz C.E., Kautz T.F., Lambert J.C., Lyons M.J., Mosley T.H., Mukamal K.J., Pase M.P., Portilla Fernandez E.C., Rissman R.A., Satizabal C.L., Vasan R.S., Yaqub A., Debette S., Dufouil C., Launer L.J., Kremen W.S., Longstreth W.T., Ikram M.A., Seshadri S. Meta-analysis of genome-wide association studies identifies ancestry-specific associations underlying circulating total tau levels. Commun. Biol. 2022;5(1):336. doi: 10.1038/s42003-022-03287-y. PubMed DOI PMC
Su F., Bai F., Zhang Z. Inflammatory cytokines and Alzheimer’s disease: A review from the perspective of genetic polymorphisms. Neurosci. Bull. 2016;32(5):469–480. doi: 10.1007/s12264-016-0055-4. PubMed DOI PMC
Ulhaq Z.S., Garcia C.P. Inflammation-related gene polymorphisms associated with Parkinson’s disease: An updated meta-analysis. Egypt. J. Med. Hum. Genet. 2020;21(1):14. doi: 10.1186/s43042-020-00056-6. DOI
Li X., Zhang D.F., Bi R., Tan L.W., Chen X., Xu M., Yao Y.G. Convergent transcriptomic and genomic evidence supporting a dysregulation of CXCL16 and CCL5 in Alzheimer’s disease. Alzheimers Res. Ther. 2023;15(1):17. doi: 10.1186/s13195-022-01159-5. PubMed DOI PMC
Pedersen C.C., Lange J., Førland M.G.G., Macleod A.D., Alves G., Maple-Grødem J. A systematic review of associations between common SNCA variants and clinical heterogeneity in Parkinson’s disease. NPJ Parkinsons Dis. 2021;7(1):54. doi: 10.1038/s41531-021-00196-5. PubMed DOI PMC
Hollenbach J.A., Norman P.J., Creary L.E., Damotte V., Montero-Martin G., Caillier S., Anderson K.M., Misra M.K., Nemat-Gorgani N., Osoegawa K., Santaniello A., Renschen A., Marin W.M., Dandekar R., Parham P., Tanner C.M., Hauser S.L., Fernandez-Viña M., Oksenberg J.R. A specific amino acid motif of HLA-DRB1 mediates risk and interacts with smoking history in Parkinson’s disease. Proc. Natl. Acad. Sci. 2019;116(15):7419–7424. doi: 10.1073/pnas.1821778116. PubMed DOI PMC
Yu E., Ambati A., Andersen M.S., Krohn L., Estiar M.A., Saini P., Senkevich K., Sosero Y.L., Sreelatha A.A.K., Ruskey J.A., Asayesh F., Spiegelman D., Toft M., Viken M.K., Sharma M., Blauwendraat C., Pihlstrøm L., Mignot E., Gan-Or Z. Fine mapping of the HLA locus in Parkinson’s disease in Europeans. NPJ Parkinsons Dis. 2021;7(1):84. doi: 10.1038/s41531-021-00231-5. PubMed DOI PMC
Harms A.S., Ferreira S.A., Romero-Ramos M. Periphery and brain, innate and adaptive immunity in Parkinson’s disease. Acta Neuropathol. 2021;141(4):527–545. doi: 10.1007/s00401-021-02268-5. PubMed DOI PMC
Yi M., Li J., Jian S., Li B., Huang Z., Shu L., Zhang Y. Quantitative and causal analysis for inflammatory genes and the risk of Parkinson’s disease. Front. Immunol. 2023;14:1119315. doi: 10.3389/fimmu.2023.1119315. PubMed DOI PMC
Abbott N.J., Patabendige A.A.K., Dolman D.E.M., Yusof S.R., Begley D.J. Structure and function of the blood–brain barrier. Neurobiol. Dis. 2010;37(1):13–25. doi: 10.1016/j.nbd.2009.07.030. PubMed DOI
Labzin L.I., Heneka M.T., Latz E. Innate immunity and neurodegeneration. Annu. Rev. Med. 2018;69(1):437–449. doi: 10.1146/annurev-med-050715-104343. PubMed DOI
Huang X., Hussain B., Chang J. Peripheral inflammation and blood–brain barrier disruption: Effects and mechanisms. CNS Neurosci. Ther. 2021;27(1):36–47. doi: 10.1111/cns.13569. PubMed DOI PMC
Wilhelm I., Nyúl-Tóth Á., Suciu M., Hermenean A., Krizbai I.A. Heterogeneity of the blood-brain barrier. Tissue Barriers. 2016;4(1):e1143544. doi: 10.1080/21688370.2016.1143544. PubMed DOI PMC
Mayne K., White J.A., McMurran C.E., Rivera F.J., de la Fuente A.G. Aging and neurodegenerative disease: Is the adaptive immune system a friend or foe? Front. Aging Neurosci. 2020;12:572090. doi: 10.3389/fnagi.2020.572090. PubMed DOI PMC
Glass C.K., Saijo K., Winner B., Marchetto M.C., Gage F.H. Mechanisms underlying inflammation in neurodegeneration. Cell. 2010;140(6):918–934. doi: 10.1016/j.cell.2010.02.016. PubMed DOI PMC
Stephenson J., Nutma E., van der Valk P., Amor S. Inflammation in CNS neurodegenerative diseases. Immunology. 2018;154(2):204–219. doi: 10.1111/imm.12922. PubMed DOI PMC
Fathi M., Vakili K., Yaghoobpoor S., Qadirifard M.S., Kosari M., Naghsh N.; Asgari taei, A.; Klegeris, A.; Dehghani, M.; Bahrami, A.; Taheri, H.; Mohamadkhani, A.; Hajibeygi, R.; Rezaei Tavirani, M.; Sayehmiri, F. Pre-clinical studies identifying molecular pathways of neuroinflammation in Parkinson’s disease: A systematic review. Front. Aging Neurosci. 2022;14:855776. doi: 10.3389/fnagi.2022.855776. PubMed DOI PMC
Gorecki A.M., Anyaegbu C.C., Anderton R.S. TLR2 and TLR4 in Parkinson’s disease pathogenesis: The environment takes a toll on the gut. Transl. Neurodegener. 2021;10(1):47. doi: 10.1186/s40035-021-00271-0. PubMed DOI PMC
Bellucci A., Bubacco L., Longhena F., Parrella E., Faustini G., Porrini V., Bono F., Missale C., Pizzi M. Nuclear Factor-κB dysregulation and α-synuclein pathology: Critical interplay in the pathogenesis of Parkinson’s disease. Front. Aging Neurosci. 2020;12:68. doi: 10.3389/fnagi.2020.00068. PubMed DOI PMC
Juranek J., Mukherjee K., Kordas B.; Załęcki, M.; Korytko, A.; Zglejc-Waszak, K.; Szuszkiewicz, J.; Banach, M. Role of RAGE in the pathogenesis of neurological disorders. Neurosci. Bull. 2022;38(10):1248–1262. doi: 10.1007/s12264-022-00878-x. PubMed DOI PMC
Spulber S., Bartfai T., Schultzberg M. IL-1/IL-1ra balance in the brain revisited: Evidence from transgenic mouse models. Brain Behav. Immun. 2009;23(5):573–579. doi: 10.1016/j.bbi.2009.02.015. PubMed DOI
Bai H., Zhang Q. Activation of NLRP3 inflammasome and onset of Alzheimer’s disease. Front. Immunol. 2021;12:701282. doi: 10.3389/fimmu.2021.701282. PubMed DOI PMC
Martin-Ruiz C., Williams-Gray C.H., Yarnall A.J., Boucher J.J., Lawson R.A., Wijeyekoon R.S., Barker R.A., Kolenda C., Parker C., Burn D.J., Von Zglinicki T., Saretzki G. Senescence and inflammatory markers for predicting clinical progression in Parkinson’s disease: The ICICLE-PD Study. J. Parkinsons Dis. 2020;10(1):193–206. doi: 10.3233/JPD-191724. PubMed DOI PMC
Lara P.C., Macías-Verde D., Burgos-Burgos J. Age-induced NLRP3 inflammasome over-activation increases lethality of SARS-CoV-2 pneumonia in elderly patients. Aging Dis. 2020;11(4):756–762. doi: 10.14336/AD.2020.0601. PubMed DOI PMC
Stout-Delgado H.W., Vaughan S.E., Shirali A.C., Jaramillo R.J., Harrod K.S. Impaired NLRP3 inflammasome function in elderly mice during influenza infection is rescued by treatment with nigericin. J. Immunol. 2012;188(6):2815–2824. doi: 10.4049/jimmunol.1103051. PubMed DOI PMC
Nagatsu T., Mogi M., Ichinose H., Togari A. Changes in cytokines and neurotrophins in Parkinson’s disease. J. Neural Transm. Suppl. 2000;(60):277–290. doi: 10.1007/978-3-7091-6301-6_19. PubMed DOI
Zhang P., Shao X.Y., Qi G.J., Chen Q., Bu L.L., Chen L.J., Shi J., Ming J., Tian B. Cdk5-dependent activation of neuronal inflammasomes in Parkinson’s disease. Mov. Disord. 2016;31(3):366–376. doi: 10.1002/mds.26488. PubMed DOI
Kitazawa M., Cheng D., Tsukamoto M.R., Koike M.A., Wes P.D., Vasilevko V., Cribbs D.H., LaFerla F.M. Blocking IL-1 signaling rescues cognition, attenuates tau pathology, and restores neuronal β-catenin pathway function in an Alzheimer’s disease model. J. Immunol. 2011;187(12):6539–6549. doi: 10.4049/jimmunol.1100620. PubMed DOI PMC
Wang W., Nguyen L.T.T., Burlak C., Chegini F., Guo F., Chataway T., Ju S., Fisher O.S., Miller D.W., Datta D., Wu F., Wu C.X., Landeru A., Wells J.A., Cookson M.R., Boxer M.B., Thomas C.J., Gai W.P., Ringe D., Petsko G.A., Hoang Q.Q. Caspase-1 causes truncation and aggregation of the Parkinson’s disease-associated protein α-synuclein. Proc. Natl. Acad. Sci. 2016;113(34):9587–9592. doi: 10.1073/pnas.1610099113. PubMed DOI PMC
Hurelbrink C.B., Armstrong R.J.E., Luheshi L.M., Dunnett S.B., Rosser A.E., Barker R.A. Death of dopaminergic neurons in vitro and in nigral grafts: Reevaluating the role of caspase activation. Exp. Neurol. 2001;171(1):46–58. doi: 10.1006/exnr.2001.7749. PubMed DOI
Caputi V., Giron M. Microbiome-gut-brain axis and toll-like receptors in Parkinson’s disease. Int. J. Mol. Sci. 2018;19(6):1689. doi: 10.3390/ijms19061689. PubMed DOI PMC
Howe A.M., Burke S., O’Reilly M.E., McGillicuddy F.C., Costello D.A. Palmitic acid and oleic acid differently modulate tlr2-mediated inflammatory responses in microglia and macrophages. Mol. Neurobiol. 2022;59(4):2348–2362. doi: 10.1007/s12035-022-02756-z. PubMed DOI PMC
Minoretti P., Gazzaruso C., Vito C.D., Emanuele E., Bianchi M., Coen E., Reino M., Geroldi D. Effect of the functional toll-like receptor 4 Asp299Gly polymorphism on susceptibility to late-onset Alzheimer’s disease. Neurosci. Lett. 2006;391(3):147–149. doi: 10.1016/j.neulet.2005.08.047. PubMed DOI
Okun E., Griffioen K.J., Lathia J.D., Tang S.C., Mattson M.P., Arumugam T.V. Toll-like receptors in neurodegeneration. Brain Res. Brain Res. Rev. 2009;59(2):278–292. doi: 10.1016/j.brainresrev.2008.09.001. PubMed DOI PMC
Liddelow S.A., Barres B.A. Reactive Astrocytes: Production, Function, and Therapeutic Potential. Immunity. 2017;46(6):957–967. doi: 10.1016/j.immuni.2017.06.006. PubMed DOI
Labib D., Wang Z., Prakash P., Zimmer M., Smith M.D., Frazel P.W., Barbar L., Sapar M.L., Calabresi P.A., Peng J., Liddelow S.A., Fossati V. Proteomic Alterations and Novel Markers of Neurotoxic Reactive Astrocytes in Human Induced Pluripotent Stem Cell Models. Front. Mol. Neurosci. 2022;15:870085. doi: 10.3389/fnmol.2022.870085. PubMed DOI PMC
Zhao Y., Bhattacharjee S., Jones B.M., Hill J., Dua P., Lukiw W.J. Regulation of neurotropic signaling by the inducible, NF-kB-sensitive miRNA-125b in Alzheimer’s disease (AD) and in primary human neuronal-glial (HNG) cells. Mol. Neurobiol. 2014;50(1):97–106. doi: 10.1007/s12035-013-8595-3. PubMed DOI PMC
Singh S., Singh T.G. Role of Nuclear Factor Kappa B (NF-κB) signalling in neurodegenerative diseases: A mechanistic approach. Curr. Neuropharmacol. 2020;18(10):918–935. doi: 10.2174/1570159X18666200207120949. PubMed DOI PMC
Dou F., Chu X., Zhang B., Liang L., Lu G., Ding J., Chen S. EriB targeted inhibition of microglia activity attenuates MPP+ induced DA neuron injury through the NF-κB signaling pathway. Mol. Brain. 2018;11(1):75. doi: 10.1186/s13041-018-0418-z. PubMed DOI PMC
Rauf A., Badoni H., Abu-Izneid T., Olatunde A., Rahman M.M., Painuli S., Semwal P., Wilairatana P., Mubarak M.S. Neuroinflammatory markers: Key indicators in the pathology of neurodegenerative diseases. Molecules. 2022;27(10):3194. doi: 10.3390/molecules27103194. PubMed DOI PMC
Huang Y., Erdmann N., Peng H., Zhao Y., Zheng J. The role of TNF related apoptosis-inducing ligand in neurodegenerative diseases. Cell. Mol. Immunol. 2005;2(2):113–122. PubMed
Uberti D., Cantarella G., Facchetti F., Cafici A., Grasso G., Bernardini R., Memo M. TRAIL is expressed in the brain cells of Alzheimer’s disease patients. Neuroreport. 2004;15(4):579–581. PubMed
Akiyama H., Barger S., Barnum S., Bradt B., Bauer J., Cole G.M., Cooper N.R., Eikelenboom P., Emmerling M., Fiebich B.L., Finch C.E., Frautschy S., Griffin W.S., Hampel H., Hull M., Landreth G., Lue L., Mrak R., Mackenzie I.R., McGeer P.L., O’Banion M.K., Pachter J., Pasinetti G., Plata-Salaman C., Rogers J., Rydel R., Shen Y., Streit W., Strohmeyer R., Tooyoma I., Van Muiswinkel F.L., Veerhuis R., Walker D., Webster S., Wegrzyniak B., Wenk G., Wyss-Coray T. Inflammation and Alzheimer’s disease. Neurobiol. Aging. 2000;21(3):383–421. doi: 10.1016/S0197-4580(00)00124-X. PubMed DOI PMC
Tarkowski E., Liljeroth A.M., Nilsson Å., Minthon L., Blennow K. Decreased levels of intrathecal interleukin 1 receptor antagonist in Alzheimer’s disease. Dement. Geriatr. Cogn. Disord. 2001;12(5):314–317. doi: 10.1159/000051276. PubMed DOI
He P., Zhong Z., Lindholm K., Berning L., Lee W., Lemere C., Staufenbiel M., Li R., Shen Y. Deletion of tumor necrosis factor death receptor inhibits amyloid β generation and prevents learning and memory deficits in Alzheimer’s mice. J. Cell Biol. 2007;178(5):829–841. doi: 10.1083/jcb.200705042. PubMed DOI PMC
Hickman S.E., Allison E.K., El Khoury J. Microglial dysfunction and defective beta-amyloid clearance pathways in aging Alzheimer’s disease mice. J. Neurosci. 2008;28(33):8354–8360. doi: 10.1523/JNEUROSCI.0616-08.2008. PubMed DOI PMC
Nutma E., van Gent D., Amor S., Peferoen L.A.N. Astrocyte and oligodendrocyte cross-talk in the central nervous system. Cells. 2020;9(3):600. doi: 10.3390/cells9030600. PubMed DOI PMC
Santoro A., Spinelli C.C., Martucciello S., Nori S.L., Capunzo M., Puca A.A., Ciaglia E. Innate immunity and cellular senescence: The good and the bad in the developmental and aged brain. J. Leukoc. Biol. 2018;103(3):509–524. doi: 10.1002/JLB.3MR0118-003R. PubMed DOI
Tan Z.S., Beiser A.S., Vasan R.S., Roubenoff R., Dinarello C.A., Harris T.B., Benjamin E.J., Au R., Kiel D.P., Wolf P.A., Seshadri S. Inflammatory markers and the risk of Alzheimer disease: The Framingham Study. Neurology. 2007;68(22):1902–1908. doi: 10.1212/01.wnl.0000263217.36439.da. PubMed DOI
Burré J., Sharma M., Südhof T.C. Cell biology and pathophysiology of α-synuclein. Cold Spring Harb. Perspect. Med. 2018;8(3):a024091. doi: 10.1101/cshperspect.a024091. PubMed DOI PMC
Nakanishi H. Microglial cathepsin B as a key driver of inflammatory brain diseases and brain aging. Neural Regen. Res. 2020;15(1):25–29. doi: 10.4103/1673-5374.264444. PubMed DOI PMC
Kim C., Ho D.H., Suk J.E., You S., Michael S., Kang J., Joong Lee S., Masliah E., Hwang D., Lee H.J., Lee S.J. Neuron-released oligomeric α-synuclein is an endogenous agonist of TLR2 for paracrine activation of microglia. Nat. Commun. 2013;4(1):1562. doi: 10.1038/ncomms2534. PubMed DOI PMC
Xie Y.X., Naseri N.N., Fels J., Kharel P., Na Y., Lane D., Burré J., Sharma M. Lysosomal exocytosis releases pathogenic α-synuclein species from neurons in synucleinopathy models. Nat. Commun. 2022;13(1):4918. doi: 10.1038/s41467-022-32625-1. PubMed DOI PMC
Lashuel H.A., Overk C.R., Oueslati A., Masliah E. The many faces of α-synuclein: from structure and toxicity to therapeutic target. Nat. Rev. Neurosci. 2013;14(1):38–48. doi: 10.1038/nrn3406. PubMed DOI PMC
Bendor J.T., Logan T.P., Edwards R.H. The function of α-synuclein. Neuron. 2013;79(6):1044–1066. doi: 10.1016/j.neuron.2013.09.004. PubMed DOI PMC
Soraci L., Gambuzza M.E., Biscetti L., Laganà P., Lo Russo C., Buda A., Barresi G., Corsonello A., Lattanzio F., Lorello G., Filippelli G., Marino S. Toll-like receptors and NLRP3 inflammasome-dependent pathways in Parkinson’s disease: Mechanisms and therapeutic implications. J. Neurol. 2023;270(3):1346–1360. doi: 10.1007/s00415-022-11491-3. PubMed DOI PMC
Volpicelli-Daley L., Brundin P. Prion-like propagation of pathology in Parkinson disease. Handb. Clin. Neurol. 2018;153:321–335. doi: 10.1016/B978-0-444-63945-5.00017-9. PubMed DOI PMC
Noguchi-Shinohara M., Ono K. The mechanisms of the roles of α-synuclein, amyloid-β, and tau protein in the lewy body diseases: pathogenesis, early detection, and therapeutics. Int. J. Mol. Sci. 2023;24(12):10215. doi: 10.3390/ijms241210215. PubMed DOI PMC
Schrag A. Psychiatric aspects of Parkinson’s disease. J. Neurol. 2004;251(7):795–804. doi: 10.1007/s00415-004-0483-3. PubMed DOI
Subramanian A., Tamilanban T., Alsayari A., Ramachawolran G., Wong L.S., Sekar M., Gan S.H., Subramaniyan V., Chinni S.V., Izzati Mat Rani N.N., Suryadevara N., Wahab S. Trilateral association of autophagy, mTOR and Alzheimer’s disease: Potential pathway in the development for Alzheimer’s disease therapy. Front. Pharmacol. 2022;13:1094351. doi: 10.3389/fphar.2022.1094351. PubMed DOI PMC
Kostiuchenko O., Lushnikova I., Kowalczyk M., Skibo G. mTOR/α-ketoglutarate-mediated signaling pathways in the context of brain neurodegeneration and neuroprotection. BBA Adv. 2022;2:100066. doi: 10.1016/j.bbadva.2022.100066. PubMed DOI PMC
Blagov A.V., Grechko A.V., Nikiforov N.G., Borisov E.E., Sadykhov N.K., Orekhov A.N. Role of impaired mitochondrial dynamics processes in the pathogenesis of Alzheimer’s disease. Int. J. Mol. Sci. 2022;23(13):6954. doi: 10.3390/ijms23136954. PubMed DOI PMC
Ikeda-Matsuo Y., Miyata H., Mizoguchi T., Ohama E., Naito Y., Uematsu S., Akira S., Sasaki Y., Tanabe M. Microsomal prostaglandin E synthase-1 is a critical factor in dopaminergic neurodegeneration in Parkinson’s disease. Neurobiol. Dis. 2019;124:81–92. doi: 10.1016/j.nbd.2018.11.004. PubMed DOI
Mi Y., Qi G., Vitali F., Shang Y., Raikes A.C., Wang T., Jin Y., Brinton R.D., Gu H., Yin F. Loss of fatty acid degradation by astrocytic mitochondria triggers neuroinflammation and neurodegeneration. Nat. Metab. 2023;5(3):445–465. doi: 10.1038/s42255-023-00756-4. PubMed DOI PMC
Kulminski A.M., Jain-Washburn E., Loiko E., Loika Y., Feng F., Culminskaya I. Associations of the APOE ε2 and ε4 alleles and polygenic profiles comprising APOE-TOMM40-APOC1 variants with Alzheimer’s disease biomarkers. Aging. 2022;14(24):9782–9804. doi: 10.18632/aging.204384. PubMed DOI PMC
Mu G., Ren C., Zhang Y., Lu B., Feng J., Wu D., Xu X., Ou C. Amelioration of central neurodegeneration by docosahexaenoic acid in trigeminal neuralgia rats through the regulation of central neuroinflammation. Int. Immunopharmacol. 2023;114:109544. doi: 10.1016/j.intimp.2022.109544. PubMed DOI
Xie A., Ensink E., Li P.; Gordevičius, J.; Marshall, L.L.; George, S.; Pospisilik, J.A.; Aho, V.T.E.; Houser, M.C.; Pereira, P.A.B.; Rudi, K.; Paulin, L.; Tansey, M.G.; Auvinen, P.; Brundin, P.; Brundin, L.; Labrie, V.; Scheperjans, F. Bacterial butyrate in parkinson’s disease is linked to epigenetic changes and depressive symptoms. Mov. Disord. 2022;37(8):1644–1653. doi: 10.1002/mds.29128. PubMed DOI PMC
Verhaar B.J.H., Hendriksen H.M.A., de Leeuw F.A., Doorduijn A.S., van Leeuwenstijn M., Teunissen C.E., Barkhof F., Scheltens P., Kraaij R., van Duijn C.M., Nieuwdorp M., Muller M., van der Flier W.M. Gut microbiota composition is related to ad pathology. Front. Immunol. 2022;12:794519. doi: 10.3389/fimmu.2021.794519. PubMed DOI PMC
Cammann D., Lu Y., Cummings M.J., Zhang M.L., Cue J.M., Do J., Ebersole J., Chen X., Oh E.C., Cummings J.L., Chen J. Genetic correlations between Alzheimer’s disease and gut microbiome genera. Sci. Rep. 2023;13(1):5258. doi: 10.1038/s41598-023-31730-5. PubMed DOI PMC
Lang Y., Chu F., Shen D., Zhang W., Zheng C., Zhu J., Cui L. Role of inflammasomes in neuroimmune and neurodegenerative diseases: A systematic review. Mediators Inflamm. 2018;2018:1–11. doi: 10.1155/2018/1549549. PubMed DOI PMC
Miao J., Ma H., Yang Y., Liao Y., Lin C., Zheng J., Yu M., Lan J. Microglia in Alzheimer’s disease: Pathogenesis, mechanisms, and therapeutic potentials. Front. Aging Neurosci. 2023;15:1201982. doi: 10.3389/fnagi.2023.1201982. PubMed DOI PMC
Wes P.D., Holtman I.R., Boddeke E.W.G.M., Möller T., Eggen B.J.L. Next generation transcriptomics and genomics elucidate biological complexity of microglia in health and disease. Glia. 2016;64(2):197–213. doi: 10.1002/glia.22866. PubMed DOI
Holtman I.R., Raj D.D., Miller J.A., Schaafsma W., Yin Z., Brouwer N., Wes P.D., Möller T., Orre M., Kamphuis W., Hol E.M., Boddeke E.W.G.M., Eggen B.J.L. Induction of a common microglia gene expression signature by aging and neurodegenerative conditions: A co-expression meta-analysis. Acta Neuropathol. Commun. 2015;3(1):31. doi: 10.1186/s40478-015-0203-5. PubMed DOI PMC
Pan J., Ma N., Yu B., Zhang W., Wan J. Transcriptomic profiling of microglia and astrocytes throughout aging. J. Neuroinflammation. 2020;17(1):97. doi: 10.1186/s12974-020-01774-9. PubMed DOI PMC
Spurrier J., Nicholson L., Fang X.T., Stoner A.J., Toyonaga T., Holden D., Siegert T.R., Laird W., Allnutt M.A., Chiasseu M., Brody A.H., Takahashi H., Nies S.H., Cañamás A.P., Sadasivam P., Lee S., Li S., Zhang L., Huang Y.H., Carson R.E., Cai Z., Strittmatter S.M. Reversal of synapse loss in Alzheimer mouse models by targeting mGluR5 to prevent synaptic tagging by C1Q. Sci. Transl. Med. 2022;14(647):eabi8593. doi: 10.1126/scitranslmed.abi8593. PubMed DOI PMC
Balog B.M., Sonti A., Zigmond R.E. Neutrophil biology in injuries and diseases of the central and peripheral nervous systems. Prog. Neurobiol. 2023;228:102488. doi: 10.1016/j.pneurobio.2023.102488. PubMed DOI PMC
Aries M.L., Hensley-McBain T. Neutrophils as a potential therapeutic target in Alzheimer’s disease. Front. Immunol. 2023;14:1123149. doi: 10.3389/fimmu.2023.1123149. PubMed DOI PMC
Harcha P.A., Garcés P., Arredondo C., Fernández G., Sáez J.C., van Zundert B. Mast cell and astrocyte hemichannels and their role in alzheimer’s disease, ALS, and harmful stress conditions. Int. J. Mol. Sci. 2021;22(4):1924. doi: 10.3390/ijms22041924. PubMed DOI PMC
Wang S., van de Pavert S.A. Innate lymphoid cells in the central nervous system. Front. Immunol. 2022;13:837250. doi: 10.3389/fimmu.2022.837250. PubMed DOI PMC
Brauning A., Rae M., Zhu G., Fulton E., Admasu T.D., Stolzing A., Sharma A. Aging of the immune system: Focus on natural killer cells phenotype and functions. Cells. 2022;11(6):1017. doi: 10.3390/cells11061017. PubMed DOI PMC
Prager I., Watzl C. Mechanisms of natural killer cell-mediated cellular cytotoxicity. J. Leukoc. Biol. 2019;105(6):1319–1329. doi: 10.1002/JLB.MR0718-269R. PubMed DOI
Menees K.B., Lee J.K. New insights and implications of natural killer cells in parkinson’s disease. J. Parkinsons Dis. 2022;12(s1):S83–S92. doi: 10.3233/JPD-223212. PubMed DOI PMC
Zhang L., Zhang Y., Fan D. Pathological role of natural killer cells in parkinson’s disease: A systematic review. Front. Aging Neurosci. 2022;14:890816. doi: 10.3389/fnagi.2022.890816. PubMed DOI PMC
Muñiz-Castrillo S., Vogrig A., Honnorat J. Associations between HLA and autoimmune neurological diseases with autoantibodies. Auto Immun. Highlights. 2020;11(1):2. doi: 10.1186/s13317-019-0124-6. PubMed DOI PMC
Boon B.D.C., Hoozemans J.J.M., Lopuhaä B., Eigenhuis K.N., Scheltens P., Kamphorst W., Rozemuller A.J.M., Bouwman F.H. Neuroinflammation is increased in the parietal cortex of atypical Alzheimer’s disease. J. Neuroinflammation. 2018;15(1):170. doi: 10.1186/s12974-018-1180-y. PubMed DOI PMC
Wang Z.T., Chen S.D., Xu W., Chen K.L., Wang H.F., Tan C.C., Cui M., Dong Q., Tan L., Yu J.T. Genome-wide association study identifies CD1A associated with rate of increase in plasma neurofilament light in non-demented elders. Aging. 2019;11(13):4521–4535. doi: 10.18632/aging.102066. PubMed DOI PMC
Chew H., Solomon V.A., Fonteh A.N. Involvement of lipids in Alzheimer’s disease pathology and potential therapies. Front. Physiol. 2020;11:598. doi: 10.3389/fphys.2020.00598. PubMed DOI PMC
Al-kuraishy H.M., Al-Gareeb A.I., Alexiou A., Papadakis M., Alsayegh A.A., Almohmadi N.H., Saad H.M., Batiha G.E.S. Pros and cons for statins use and risk of Parkinson’s disease: An updated perspective. Pharmacol. Res. Perspect. 2023;11(2):e01063. doi: 10.1002/prp2.1063. PubMed DOI PMC
Sulzer D., Alcalay R.N., Garretti F., Cote L., Kanter E., Agin-Liebes J., Liong C., McMurtrey C., Hildebrand W.H., Mao X., Dawson V.L., Dawson T.M., Oseroff C., Pham J., Sidney J., Dillon M.B., Carpenter C., Weiskopf D., Phillips E., Mallal S., Peters B., Frazier A., Lindestam A.C.S., Sette A. T cells from patients with Parkinson’s disease recognize α-synuclein peptides. Nature. 2017;546(7660):656–661. doi: 10.1038/nature22815. PubMed DOI PMC
Williams G.P., Schonhoff A.M., Jurkuvenaite A., Gallups N.J., Standaert D.G., Harms A.S. CD4 T cells mediate brain inflammation and neurodegeneration in a mouse model of Parkinson’s disease. Brain. 2021;144(7):2047–2059. doi: 10.1093/brain/awab103. PubMed DOI PMC
Iba M., Kim C., Sallin M., Kwon S., Verma A., Overk C., Rissman R.A., Sen R., Sen J.M., Masliah E. Neuroinflammation is associated with infiltration of T cells in Lewy body disease and α-synuclein transgenic models. J. Neuroinflammation. 2020;17(1):214. doi: 10.1186/s12974-020-01888-0. PubMed DOI PMC
Lyman M., Lloyd D.G., Ji X., Vizcaychipi M.P., Ma D. Neuroinflammation: The role and consequences. Neurosci. Res. 2014;79:1–12. doi: 10.1016/j.neures.2013.10.004. PubMed DOI
Carrasco E., Gómez de las Heras M.M., Gabandé-Rodríguez E., Desdín-Micó G., Aranda J.F., Mittelbrunn M. The role of T cells in age-related diseases. Nat. Rev. Immunol. 2022;22(2):97–111. doi: 10.1038/s41577-021-00557-4. PubMed DOI
Gate D., Saligrama N., Leventhal O., Yang A.C., Unger M.S., Middeldorp J., Chen K., Lehallier B., Channappa D., De Los Santos M.B., McBride A., Pluvinage J., Elahi F., Tam G.K.Y., Kim Y., Greicius M., Wagner A.D., Aigner L., Galasko D.R., Davis M.M., Wyss-Coray T. Clonally expanded CD8 T cells patrol the cerebrospinal fluid in Alzheimer’s disease. Nature. 2020;577(7790):399–404. doi: 10.1038/s41586-019-1895-7. PubMed DOI PMC
Mietelska-Porowska A., Wojda U. T lymphocytes and inflammatory mediators in the interplay between brain and blood in Alzheimer’s disease: Potential pools of new biomarkers. J. Immunol. Res. 2017;2017:1–17. doi: 10.1155/2017/4626540. PubMed DOI PMC
Rezai-Zadeh K., Gate D., Town T. CNS infiltration of peripheral immune cells: D-Day for neurodegenerative disease? J. Neuroimmune Pharmacol. 2009;4(4):462–475. doi: 10.1007/s11481-009-9166-2. PubMed DOI PMC
Dai L., Shen Y. Insights into Tcell dysfunction in Alzheimer’s disease. Aging Cell. 2021;20(12):e13511. doi: 10.1111/acel.13511. PubMed DOI PMC
Machhi J., Yeapuri P., Lu Y., Foster E., Chikhale R., Herskovitz J., Namminga K.L., Olson K.E., Abdelmoaty M.M., Gao J., Quadros R.M., Kiyota T., Jingjing L., Kevadiya B.D., Wang X., Liu Y., Poluektova L.Y., Gurumurthy C.B., Mosley R.L., Gendelman H.E. CD4+ effector T cells accelerate Alzheimer’s disease in mice. J. Neuroinflammation. 2021;18(1):272. doi: 10.1186/s12974-021-02308-7. PubMed DOI PMC
Monsonego A., Zota V., Karni A., Krieger J.I., Bar-Or A., Bitan G., Budson A.E., Sperling R., Selkoe D.J., Weiner H.L. Increased T cell reactivity to amyloid β protein in older humans and patients with Alzheimer disease. J. Clin. Invest. 2003;112(3):415–422. doi: 10.1172/JCI200318104. PubMed DOI PMC
Kustrimovic N., Comi C., Magistrelli L., Rasini E., Legnaro M., Bombelli R., Aleksic I., Blandini F., Minafra B., Riboldazzi G., Sturchio A., Mauri M., Bono G., Marino F., Cosentino M. Parkinson’s disease patients have a complex phenotypic and functional Th1 bias: Cross-sectional studies of CD4+ Th1/Th2/T17 and Treg in drug-naïve and drug-treated patients. J. Neuroinflammation. 2018;15(1):205. doi: 10.1186/s12974-018-1248-8. PubMed DOI PMC
Saunders J.A.H., Estes K.A., Kosloski L.M., Allen H.E., Dempsey K.M., Torres-Russotto D.R., Meza J.L., Santamaria P.M., Bertoni J.M., Murman D.L., Ali H.H., Standaert D.G., Mosley R.L., Gendelman H.E. CD4+ regulatory and effector/memory T cell subsets profile motor dysfunction in Parkinson’s disease. J. Neuroimmune Pharmacol. 2012;7(4):927–938. doi: 10.1007/s11481-012-9402-z. PubMed DOI PMC
Xu Y., Li Y., Wang C., Han T., Liu H., Sun L., Hong J., Hashimoto M., Wei J. The reciprocal interactions between microglia and T cells in Parkinson’s disease: A double-edged sword. J. Neuroinflammation. 2023;20(1):33. doi: 10.1186/s12974-023-02723-y. PubMed DOI PMC
Vacinova G., Vejražkova D., Rusina R., Holmerová I.; Vaňková, H.; Jarolímová, E.; Včelák, J.; Bendlová, B.; Vaňková, M. Regulated upon activation, normal T cell expressed and secreted (RANTES) levels in the peripheral blood of patients with Alzheimer’s disease. Neural Regen. Res. 2021;16(4):796–800. doi: 10.4103/1673-5374.295340. PubMed DOI PMC
Schwartz M., Baruch K. Breaking peripheral immune tolerance to CNS antigens in neurodegenerative diseases: Boosting autoimmunity to fight-off chronic neuroinflammation. J. Autoimmun. 2014;54:8–14. doi: 10.1016/j.jaut.2014.08.002. PubMed DOI
Chen X., Firulyova M., Manis M., Herz J., Smirnov I., Aladyeva E., Wang C., Bao X., Finn M.B., Hu H., Shchukina I., Kim M.W., Yuede C.M., Kipnis J., Artyomov M.N., Ulrich J.D., Holtzman D.M. Microglia-mediated T cell infiltration drives neurodegeneration in tauopathy. Nature. 2023;615(7953):668–677. doi: 10.1038/s41586-023-05788-0. PubMed DOI PMC
Subbarayan M.S., Hudson C., Moss L.D., Nash K.R., Bickford P.C. T cell infiltration and upregulation of MHCII in microglia leads to accelerated neuronal loss in an α-synuclein rat model of Parkinson’s disease. J. Neuroinflammation. 2020;17(1):242. doi: 10.1186/s12974-020-01911-4. PubMed DOI PMC
Cai H.Y., Fu X.X., Jiang H., Han S. Adjusting vascular permeability, leukocyte infiltration, and microglial cell activation to rescue dopaminergic neurons in rodent models of Parkinson’s disease. NPJ Parkinsons Dis. 2021;7(1):91. doi: 10.1038/s41531-021-00233-3. PubMed DOI PMC
Liu Y., Sorce S., Nuvolone M., Domange J., Aguzzi A. Lymphocyte activation gene 3 (Lag3) expression is increased in prion infections but does not modify disease progression. Sci. Rep. 2018;8(1):14600. doi: 10.1038/s41598-018-32712-8. PubMed DOI PMC
Guo W., Zhou M., Qiu J., Lin Y., Chen X., Huang S., Mo M., Liu H., Peng G., Zhu X., Xu P. Association of LAG3 genetic variation with an increased risk of PD in Chinese female population. J. Neuroinflammation. 2019;16(1):270. doi: 10.1186/s12974-019-1654-6. PubMed DOI PMC
García-Martín E., Pastor P., Gómez-Tabales J., Alonso-Navarro H., Alvarez I., Buongiorno M., Cerezo-Arias M.O., Aguilar M., Agúndez J.A.G., Jiménez-Jiménez F.J. Association between LAG3/CD4 gene variants and risk of Parkinson’s disease. Eur. J. Clin. Invest. 2022;52(11):e13847. doi: 10.1111/eci.13847. PubMed DOI PMC
Cui S., Du J.J., Liu S.H., Meng J., Lin Y.Q., Li G., He Y.X., Zhang P.C., Chen S., Wang G. Serum soluble lymphocyte activation gene3 as a diagnostic biomarker in Parkinson’s disease: A pilot multicenter study. Mov. Disord. 2019;34(1):138–141. doi: 10.1002/mds.27569. PubMed DOI
Roy A., Choudhury S., Banerjee R., Basu P., Kumar H. Soluble LAG-3 and Toll-interacting protein: Novel upstream neuro-inflammatory markers in Parkinson’s disease. Parkinsonism Relat. Disord. 2021;91:121–123. doi: 10.1016/j.parkreldis.2021.09.019. PubMed DOI
Saresella M., Calabrese E., Marventano I., Piancone F., Gatti A., Calvo M.G., Nemni R., Clerici M. PD1 negative and PD1 positive CD4+ T regulatory cells in mild cognitive impairment and Alzheimer’s disease. J. Alzheimers Dis. 2010;21(3):927–938. doi: 10.3233/JAD-2010-091696. PubMed DOI
Olson K.E., Mosley R.L., Gendelman H.E. The potential for treg-enhancing therapies in nervous system pathologies. Clin. Exp. Immunol. 2022:uxac084. PubMed PMC
Beers D.R., Zhao W., Wang J., Zhang X., Wen S., Neal D., Thonhoff J.R., Alsuliman A.S., Shpall E.J., Rezvani K., Appel S.H. ALS patients’ regulatory T lymphocytes are dysfunctional, and correlate with disease progression rate and severity. JCI Insight. 2017;2(5):e89530. doi: 10.1172/jci.insight.89530. PubMed DOI PMC
Schröder J.B., Pawlowski M., Meyer zu Hörste G., Gross C.C., Wiendl H., Meuth S.G., Ruck T., Warnecke T. Immune cell activation in the cerebrospinal fluid of patients with Parkinson’s disease. Front. Neurol. 2018;9:1081. doi: 10.3389/fneur.2018.01081. PubMed DOI PMC
Stym-Popper G., Matta K., Chaigneau T., Rupra R., Demetriou A., Fouquet S., Dansokho C., Toly-Ndour C., Dorothée G. Regulatory T cells decrease C3-positive reactive astrocytes in Alzheimer-like pathology. J. Neuroinflammation. 2023;20(1):64. doi: 10.1186/s12974-023-02702-3. PubMed DOI PMC
Ciccocioppo F., Lanuti P., Pierdomenico L., Simeone P., Bologna G., Ercolino E., Buttari F., Fantozzi R., Thomas A., Onofrj M., Centonze D., Miscia S., Marchisio M. The characterization of regulatory t-cell profiles in Alzheimer’s disease and multiple sclerosis. Sci. Rep. 2019;9(1):8788. doi: 10.1038/s41598-019-45433-3. PubMed DOI PMC
Baruch K., Rosenzweig N., Kertser A., Deczkowska A., Sharif A.M., Spinrad A., Tsitsou-Kampeli A., Sarel A., Cahalon L., Schwartz M. Breaking immune tolerance by targeting Foxp3+ regulatory T cells mitigates Alzheimer’s disease pathology. Nat. Commun. 2015;6(1):7967. doi: 10.1038/ncomms8967. PubMed DOI PMC
Novakova Martinkova J., Ferretti M.T., Ferrari A., Lerch O., Matuskova V., Secnik J., Hort J. Longitudinal progression of choroid plexus enlargement is associated with female sex, cognitive decline and ApoE E4 homozygote status. Front. Psychiatry. 2023;14:1039239. doi: 10.3389/fpsyt.2023.1039239. PubMed DOI PMC
Yang H., Park S.Y., Baek H., Lee C., Chung G., Liu X., Lee J.H., Kim B., Kwon M., Choi H., Kim H.J., Kim J.Y., Kim Y., Lee Y.S., Lee G., Kim S.K., Kim J.S., Chang Y.T., Jung W.S., Kim K.H., Bae H. Adoptive therapy with amyloid-β specific regulatory T cells alleviates Alzheimer’s disease. Theranostics. 2022;12(18):7668–7680. doi: 10.7150/thno.75965. PubMed DOI PMC
Moore J.R., Hubler S.L., Nelson C.D., Nashold F.E., Spanier J.A., Hayes C.E. 1,25-Dihydroxyvitamin D3 increases the methionine cycle, CD4+ T cell DNA methylation and Helios+Foxp3+ T regulatory cells to reverse autoimmune neurodegenerative disease. J. Neuroimmunol. 2018;324:100–114. doi: 10.1016/j.jneuroim.2018.09.008. PubMed DOI
Janjusevic M., Gagno G., Fluca A.L., Padoan L., Beltrami A.P., Sinagra G., Moretti R., Aleksova A. The peculiar role of vitamin D in the pathophysiology of cardiovascular and neurodegenerative diseases. Life Sci. 2022;289:120193. doi: 10.1016/j.lfs.2021.120193. PubMed DOI
Shi Y., Wei B., Li L., Wang B., Sun M. Th17 cells and inflammation in neurological disorders: Possible mechanisms of action. Front. Immunol. 2022;13:932152. doi: 10.3389/fimmu.2022.932152. PubMed DOI PMC
Sommer A., Marxreiter F., Krach F., Fadler T., Grosch J., Maroni M., Graef D., Eberhardt E., Riemenschneider M.J., Yeo G.W., Kohl Z., Xiang W., Gage F.H., Winkler J., Prots I., Winner B. Th17 lymphocytes induce neuronal cell death in a human iPSC-based model of Parkinson’s disease. Cell Stem Cell. 2019;24(6):1006. doi: 10.1016/j.stem.2019.04.019. PubMed DOI
Li J. Zhao, J.; Chen, L.; Gao, H.; Zhang, J.; Wang, D.; Zou, Y.; Qin, Q.; Qu, Y.; Li, J.; Xiong, Y.; Min, Z.; Yan, M.; Mao, Z.; Xue, Z. α-Synuclein induces Th17 differentiation and impairs the function and stability of Tregs by promoting RORC transcription in Parkinson’s disease. Brain Behav. Immun. 2023;108:32–44. doi: 10.1016/j.bbi.2022.10.023. PubMed DOI
Mohammadi S., V.; Ravari, A.; Mirzaei, T.; Zare-Bidaki, M.; Asadikaram, G.; Arababadi, M.K. IL-17A and IL-23: Plausible risk factors to induce age-associated inflammation in Alzheimer’s disease. Immunol. Invest. 2018;47(8):812–822. doi: 10.1080/08820139.2018.1504300. PubMed DOI
Biragyn A., Aliseychik M., Rogaev E. Potential importance of B cells in aging and aging-associated neurodegenerative diseases. Semin. Immunopathol. 2017;39(3):283–294. doi: 10.1007/s00281-016-0615-8. PubMed DOI PMC
Sabatino J.J., Jr, Pröbstel A.K., Zamvil S.S. B cells in autoimmune and neurodegenerative central nervous system diseases. Nat. Rev. Neurosci. 2019;20(12):728–745. doi: 10.1038/s41583-019-0233-2. PubMed DOI
Orr C.F., Rowe D.B., Mizuno Y., Mori H., Halliday G.M. A possible role for humoral immunity in the pathogenesis of Parkinson’s disease. Brain. 2005;128(11):2665–2674. doi: 10.1093/brain/awh625. PubMed DOI
Du Y., Dodel R., Hampel H., Buerger K., Lin S., Eastwood B., Bales K., Gao F., Moeller H.J., Oertel W., Farlow M., Paul S. Reduced levels of amyloid -peptide antibody in Alzheimer disease. Neurology. 2001;57(5):801–805. doi: 10.1212/WNL.57.5.801. PubMed DOI
Hyman B.T., Smith C., Buldyrev I., Whelan C., Brown H., Tang M.X., Mayeux R. Autoantibodies to amyloid-? and Alzheimer’s disease. Ann. Neurol. 2001;49(6):808–810. doi: 10.1002/ana.1061. PubMed DOI
Weksler M.E., Relkin N., Turkenich R., LaRusse S., Zhou L., Szabo P. Patients with Alzheimer disease have lower levels of serum anti-amyloid peptide antibodies than healthy elderly individuals. Exp. Gerontol. 2002;37(7):943–948. doi: 10.1016/S0531-5565(02)00029-3. PubMed DOI
DeMarshall C.A., Viviano J., Emrani S., Thayasivam U., Godsey G.A., Sarkar A., Belinka B., Libon D.J., Nagele R.G. Early detection of alzheimer’s disease-related pathology using a multi-disease diagnostic platform employing autoantibodies as blood-based biomarkers. J. Alzheimers Dis. 2023;92(3):1077–1091. doi: 10.3233/JAD-221091. PubMed DOI PMC
Carvey P.M., McRae A., Lint T.F., Ptak L.R., Lo E.S., Goetz C.G., Klawans H.L. The potential use of a dopamine neuron antibody and a striatal-derived neurotrophic factor as diagnostic markers in Parkinson’s disease. Neurology. 1991;41 doi: 10.1212/WNL.41.5_Suppl_2.53. (5, Supplement 2)(2), 53-58. PubMed DOI
Chen S., Le W.D., Xie W.J., Alexianu M.E., Engelhardt J.I., Siklós L., Appel S.H. Experimental destruction of substantia nigra initiated by Parkinson disease immunoglobulins. Arch. Neurol. 1998;55(8):1075–1080. doi: 10.1001/archneur.55.8.1075. PubMed DOI
Le W.D., Rowe D.B., Jankovic J., Xie W., Appel S.H. Effects of cerebrospinal fluid from patients with Parkinson disease on dopaminergic cells. Arch. Neurol. 1999;56(2):194–200. doi: 10.1001/archneur.56.2.194. PubMed DOI
Papachroni K.K., Ninkina N., Papapanagiotou A., Hadjigeorgiou G.M., Xiromerisiou G., Papadimitriou A., Kalofoutis A., Buchman V.L. Autoantibodies to alpha-synuclein in inherited Parkinson’s disease. J. Neurochem. 2007;101(3):749–756. doi: 10.1111/j.1471-4159.2006.04365.x. PubMed DOI PMC
Shalash A., Salama M., Makar M., Roushdy T., Elrassas H.H., Mohamed W., El-Balkimy M., Abou D.M. Elevated serum α-synuclein autoantibodies in patients with Parkinson’s disease relative to Alzheimer’s disease and controls. Front. Neurol. 2017;8:720. doi: 10.3389/fneur.2017.00720. PubMed DOI PMC
Besong-Agbo D., Wolf E., Jessen F., Oechsner M., Hametner E., Poewe W., Reindl M., Oertel W.H., Noelker C., Bacher M., Dodel R. Naturally occurring -synuclein autoantibody levels are lower in patients with Parkinson disease. Neurology. 2013;80(2):169–175. doi: 10.1212/WNL.0b013e31827b90d1. PubMed DOI
Horvath I., Iashchishyn I.A., Forsgren L., Morozova-Roche L.A. Immunochemical detection of α-synuclein autoantibodies in Parkinson’s disease: Correlation between plasma and cerebrospinal fluid levels. ACS Chem. Neurosci. 2017;8(6):1170–1176. doi: 10.1021/acschemneuro.7b00063. PubMed DOI
Akhtar R.S., Licata J.P., Luk K.C., Shaw L.M., Trojanowski J.Q., Lee V.M.Y. Measurements of auto-antibodies to α-synuclein in the serum and cerebral spinal fluids of patients with Parkinson’s disease. J. Neurochem. 2018;145(6):489–503. doi: 10.1111/jnc.14330. PubMed DOI PMC
Double K.L., Rowe D.B., Carew-Jones F.M., Hayes M., Chan D.K.Y., Blackie J., Corbett A., Joffe R., Fung V.S., Morris J., Riederer P., Gerlach M., Halliday G.M. Anti-melanin antibodies are increased in sera in Parkinson’s disease. Exp. Neurol. 2009;217(2):297–301. doi: 10.1016/j.expneurol.2009.03.002. PubMed DOI
Zappia M., Crescibene L., Bosco D., Arabia G., Nicoletti G., Bagalà A., Bastone L., Napoli I.D., Caracciolo M., Bonavita S., Di Costanzo A., Gambardella A., Quattrone A. Anti-GM1 ganglioside antibodies in Parkinson’s disease. Acta Neurol. Scand. 2002;106(1):54–57. doi: 10.1034/j.1600-0404.2002.01240.x. PubMed DOI
De Virgilio A., Greco A., Fabbrini G., Inghilleri M., Rizzo M.I., Gallo A., Conte M., Rosato C., Ciniglio Appiani M., de Vincentiis M. Parkinson’s disease: Autoimmunity and neuroinflammation. Autoimmun. Rev. 2016;15(10):1005–1011. doi: 10.1016/j.autrev.2016.07.022. PubMed DOI
Benkler M., Agmon-Levin N., Hassin-Baer S., Cohen O.S., Ortega-Hernandez O.D., Levy A., Moscavitch S.D., Szyper-Kravitz M., Damianovich M., Blank M., Chapman J., Shoenfeld Y. Immunology, autoimmunity, and autoantibodies in Parkinson’s disease. Clin. Rev. Allergy Immunol. 2012;42(2):164–171. doi: 10.1007/s12016-010-8242-y. PubMed DOI
Papuć, E.; Rejdak, K. Anti-MAG autoantibodies are increased in Parkinson’s disease but not in atypical parkinsonism. J. Neural Transm. 2017;124(2):209–216. doi: 10.1007/s00702-016-1632-4. PubMed DOI
Honorat J.A., McKeon A. Autoimmune movement disorders: A clinical and laboratory approach. Curr. Neurol. Neurosci. Rep. 2017;17(1):4. doi: 10.1007/s11910-017-0709-2. PubMed DOI
Caggiu E., Paulus K., Arru G., Piredda R., Sechi G.P., Sechi L.A. Humoral cross reactivity between α-synuclein and herpes simplex-1 epitope in Parkinson’s disease, a triggering role in the disease? J. Neuroimmunol. 2016;291:110–114. doi: 10.1016/j.jneuroim.2016.01.007. PubMed DOI
Cebrián C., Zucca F.A., Mauri P., Steinbeck J.A., Studer L., Scherzer C.R., Kanter E., Budhu S., Mandelbaum J., Vonsattel J.P., Zecca L., Loike J.D., Sulzer D. MHC-I expression renders catecholaminergic neurons susceptible to T-cell-mediated degeneration. Nat. Commun. 2014;5(1):3633. doi: 10.1038/ncomms4633. PubMed DOI PMC
Jiang T., Li G., Xu J., Gao S., Chen X. The challenge of the pathogenesis of parkinson’s disease: Is autoimmunity the culprit? Front. Immunol. 2018;9:2047. doi: 10.3389/fimmu.2018.02047. PubMed DOI PMC
Oberländer U., Pletinckx K., Döhler A., Müller N., Lutz M.B., Arzberger T., Riederer P., Gerlach M., Koutsilieri E., Scheller C. Neuromelanin is an immune stimulator for dendritic cells in vitro. BMC Neurosci. 2011;12(1):116. doi: 10.1186/1471-2202-12-116. PubMed DOI PMC
Koutsilieri E., Lutz M.B., Scheller C. Autoimmunity, dendritic cells and relevance for Parkinson’s disease. J. Neural Transm. 2013;120(1):75–81. doi: 10.1007/s00702-012-0842-7. PubMed DOI PMC
Depboylu C., Schäfer M.K.H., Arias-Carrión O., Oertel W.H., Weihe E., Höglinger G.U. Possible involvement of complement factor C1q in the clearance of extracellular neuromelanin from the substantia nigra in Parkinson disease. J. Neuropathol. Exp. Neurol. 2011;70(2):125–132. doi: 10.1097/NEN.0b013e31820805b9. PubMed DOI
Alberici A., Cristillo V., Gazzina S., Benussi A., Padovani A., Borroni B. Autoimmunity and frontotemporal dementia. Curr. Alzheimer Res. 2018;15(7):602–609. doi: 10.2174/1567205015666180119104825. PubMed DOI
Palese F., Bonomi E., Nuzzo T., Benussi A., Mellone M., Zianni E., Cisani F., Casamassa A., Alberici A., Scheggia D., Padovani A., Marcello E., Di Luca M., Pittaluga A., Usiello A., Borroni B., Gardoni F. Anti-GluA3 antibodies in frontotemporal dementia: Effects on glutamatergic neurotransmission and synaptic failure. Neurobiol. Aging. 2020;86:143–155. doi: 10.1016/j.neurobiolaging.2019.10.015. PubMed DOI
Arshad F., Varghese F., Paplikar A., Gangadhar Y., Ramakrishnan S., Chaudhuri J.R., Mahadevan A., Alladi S. Role of autoantibodies in neurodegenerative dementia: An emerging association. Dement. Geriatr. Cogn. Disord. 2021;50(2):153–160. doi: 10.1159/000517238. PubMed DOI
Maftei M., Thurm F., Schnack C., Tumani H., Otto M., Elbert T., Kolassa I.T., Przybylski M., Manea M., von Arnim C.A.F. Increased levels of antigen-bound β-amyloid autoantibodies in serum and cerebrospinal fluid of Alzheimer’s disease patients. PLoS One. 2013;8(7):e68996. doi: 10.1371/journal.pone.0068996. PubMed DOI PMC
Bartos A., Fialová L., Švarcová J. Lower serum antibodies against tau protein and heavy neurofilament in alzheimer’s disease. J. Alzheimers Dis. 2018;64(3):751–760. doi: 10.3233/JAD-180039. PubMed DOI
Koval L., Lykhmus O., Kalashnyk O., Bachinskaya N., Kravtsova G., Soldatkina M., Zouridakis M., Stergiou C., Tzartos S., Tsetlin V., Komisarenko S., Skok M. The presence and origin of autoantibodies against α4 and α7 nicotinic acetylcholine receptors in the human blood: Possible relevance to Alzheimer’s pathology. J. Alzheimers Dis. 2011;25(4):747–761. doi: 10.3233/JAD-2011-101845. PubMed DOI
Davydova T.V., Mikovskaya O.I., Fomina V.G., Voskresenskaya N.I., Doronina O.A. Induction of immune complexes and autoantibodies to serotonin and dopamine in patients with Alzheimer’s disease. Bull. Exp. Biol. Med. 2002;134(1):23–25. doi: 10.1023/A:1020692218416. PubMed DOI
Davydova T.V., Voskresenskaya N.I., Gorbatov V.Y., Fomina V.G., Doronina O.A., Maksunova I.V. Production of autoantibodies to glutamate during Alzheimer’s dementia. Bull. Exp. Biol. Med. 2009;147(4):405–407. doi: 10.1007/s10517-009-0530-2. PubMed DOI
Busse S., Brix B., Kunschmann R., Bogerts B., Stoecker W., Busse M. N-methyl-d-aspartate glutamate receptor (NMDA-R) antibodies in mild cognitive impairment and dementias. Neurosci. Res. 2014;85:58–64. doi: 10.1016/j.neures.2014.06.002. PubMed DOI
Gruden M.A., Davidova T.B., Mališauskas M., Sewell R.D.E., Voskresenskaya N.I., Wilhelm K., Elistratova E.I., Sherstnev V.V., Morozova-Roche L.A. Differential neuroimmune markers to the onset of Alzheimer’s disease neurodegeneration and dementia: Autoantibodies to Aβ(25–35) oligomers, S100b and neurotransmitters. J. Neuroimmunol. 2007;186(1-2):181–192. doi: 10.1016/j.jneuroim.2007.03.023. PubMed DOI
Mecocci P., Parnetti L., Donato R., Santucci C., Santucci A., Cadini D., Foà E., Cecchetti R., Senin U. Serum autoantibodies against glial fibrillary acidic protein in brain aging and senile dementias. Brain Behav. Immun. 1992;6(3):286–292. doi: 10.1016/0889-1591(92)90049-T. PubMed DOI
McRae A., Dahlström A., Polinsky R., Ling E.A. Cerebrospinal fluid microglial antibodies: Potential diagnostic markers for immune mechanisms in Alzheimer’s disease. Behav. Brain Res. 1993;57(2):225–234. doi: 10.1016/0166-4328(93)90139-H. PubMed DOI
Kingsley B.S., Gaskin F., Fu S.M. Human antibodies to neurofibrillary tangles and astrocytes in Alzheimer’s disease. J. Neuroimmunol. 1988;19(1-2):89–99. doi: 10.1016/0165-5728(88)90038-0. PubMed DOI
Kankaanpää J., Turunen S.P., Moilanen V., Hörkkö S., Remes A.M. Cerebrospinal fluid antibodies to oxidized LDL are increased in Alzheimer’s disease. Neurobiol. Dis. 2009;33(3):467–472. doi: 10.1016/j.nbd.2008.12.001. PubMed DOI
Vojdani A., Vojdani E. Amyloid-Beta 1-42 cross-reactive antibody prevalent in human sera may contribute to intraneuronal deposition of A-Beta-P-42. Int. J. Alzheimers Dis. 2018;2018:1–12. doi: 10.1155/2018/1672568. PubMed DOI PMC
Mruthinti S., Schade R., Harrell D., Gulati N., Swamy-Mruthinti S., Lee G., Buccafusco J. Autoimmunity in Alzheimer’s disease as evidenced by plasma immunoreactivity against RAGE and Abeta42: Complication of diabetes. Curr. Alzheimer Res. 2006;3(3):229–235. doi: 10.2174/156720506777632899. PubMed DOI
Giil L.M., Kristoffersen E.K., Vedeler C.A., Aarsland D., Nordrehaug J.E., Winblad B., Cedazo-Minguez A., Lund A., Reksten T.R. Autoantibodies toward the angiotensin 2 Type 1 receptor: A novel autoantibody in alzheimer’s disease. J. Alzheimers Dis. 2015;47(2):523–529. doi: 10.3233/JAD-150053. PubMed DOI
Colasanti T., Barbati C., Rosano G., Malorni W., Ortona E. Autoantibodies in patients with Alzheimer’s disease: Pathogenetic role and potential use as biomarkers of disease progression. Autoimmun. Rev. 2010;9(12):807–811. doi: 10.1016/j.autrev.2010.07.008. PubMed DOI
Ariga T., Jarvis W.D., Yu R.K. Role of sphingolipid-mediated cell death in neurodegenerative diseases. J. Lipid Res. 1998;39(1):1–16. doi: 10.1016/S0022-2275(20)34198-5. PubMed DOI
Jianming W., Ling L. Autoantibodies in Alzheimer’s disease: Potential biomarkers, pathogenic roles, and therapeutic implications. J. Biomed. Res. 2016;30(5):361–372. doi: 10.7555/JBR.30.20150131. PubMed DOI PMC
Vacirca D., Delunardo F., Matarrese P., Colasanti T., Margutti P., Siracusano A., Pontecorvo S., Capozzi A., Sorice M., Francia A., Malorni W., Ortona E. Autoantibodies to the adenosine triphosphate synthase play a pathogenetic role in Alzheimer’s disease. Neurobiol. Aging. 2012;33(4):753–766. doi: 10.1016/j.neurobiolaging.2010.05.013. PubMed DOI
Berry A., Vacirca D., Capoccia S., Bellisario V., Malorni W., Ortona E., Cirulli F. Anti-ATP synthase autoantibodies induce neuronal death by apoptosis and impair cognitive performance in C57BL/6J mice. J. Alzheimers Dis. 2012;33(2):317–321. doi: 10.3233/JAD-2012-121312. PubMed DOI
Dinkins M.B., Dasgupta S., Wang G., Zhu G., He Q., Kong J.N., Bieberich E. The 5XFAD mouse model of Alzheimer’s disease exhibits an age-dependent increase in anti-ceramide IgG and exogenous administration of ceramide further increases anti-ceramide titers and amyloid plaque burden. J. Alzheimers Dis. 2015;46(1):55–61. doi: 10.3233/JAD-150088. PubMed DOI PMC
Li X., Sundquist J., Sundquist K. Subsequent risks of Parkinson disease in patients with autoimmune and related disorders: A nationwide epidemiological study from Sweden. Neurodegener. Dis. 2012;10(1-4):277–284. doi: 10.1159/000333222. PubMed DOI
Li X., Sundquist J., Zöller B., Sundquist K. Dementia and Alzheimer’s disease risks in patients with autoimmune disorders. Geriatr. Gerontol. Int. 2018;18(9):1350–1355. doi: 10.1111/ggi.13488. PubMed DOI
Cho Y.Y., Kim B., Shin D.W., Youn J., Mok J.O., Kim C.H., Kim S.W., Chung J.H., Han K., Kim T.H. Graves’ disease and the risk of Parkinson’s disease: A Korean population-based study. Brain Commun. 2022;4(1):fcac014. doi: 10.1093/braincomms/fcac014. PubMed DOI PMC
Bonuccelli U., D’Avino C., Caraccio N., Del Guerra P., Casolaro A., Pavese N., Del Dotto P., Monzani F. Thyroid function and autoimmunity in Parkinson’s disease: A study of 101 patients. Parkinsonism Relat. Disord. 1999;5(1-2):49–53. doi: 10.1016/S1353-8020(99)00010-3. PubMed DOI
Charoenngam N., Rittiphairoj T., Ponvilawan B., Prasongdee K. Thyroid dysfunction and risk of Parkinson’s disease: A systematic review and meta-analysis. Front. Endocrinol. 2022;13:863281. doi: 10.3389/fendo.2022.863281. PubMed DOI PMC
Yeung C.H.C., Au Yeung S.L., Schooling C.M. Association of autoimmune diseases with Alzheimer’s disease: A mendelian randomization study. J. Psychiatr. Res. 2022;155:550–558. doi: 10.1016/j.jpsychires.2022.09.052. PubMed DOI
Ungprasert P., Wijarnpreecha K., Thongprayoon C. Rheumatoid arthritis and the risk of dementia: A systematic review and meta-analysis. Neurol. India. 2016;64(1):56–61. doi: 10.4103/0028-3886.173623. PubMed DOI
McDowell B., Marr C., Holmes C., Edwards C.J., Cardwell C., McHenry M., Meenagh G., McGuinness B. Prevalence of cognitive impairment in patients with rheumatoid arthritis: A cross sectional study. BMC Psychiatry. 2022;22(1):777. doi: 10.1186/s12888-022-04417-w. PubMed DOI PMC
Tansey M.G., Wallings R.L., Houser M.C., Herrick M.K., Keating C.E., Joers V. Inflammation and immune dysfunction in Parkinson disease. Nat. Rev. Immunol. 2022;22(11):657–673. doi: 10.1038/s41577-022-00684-6. PubMed DOI PMC
Li D., Hong X., Chen T. Association between rheumatoid arthritis and risk of Parkinson’s disease: A meta-analysis and systematic review. Front. Neurol. 2022;13:885179. doi: 10.3389/fneur.2022.885179. PubMed DOI PMC
Li M., Wan J., Xu Z., Tang B. The association between Parkinson’s disease and autoimmune diseases: A systematic review and meta-analysis. Front. Immunol. 2023;14:1103053. doi: 10.3389/fimmu.2023.1103053. PubMed DOI PMC
Policicchio S., Ahmad A.N., Powell J.F., Proitsi P. Rheumatoid arthritis and risk for Alzheimer’s disease: A systematic review and meta-analysis and a Mendelian Randomization study. Sci. Rep. 2017;7(1):12861. doi: 10.1038/s41598-017-13168-8. PubMed DOI PMC
Cooper J., Pastorello Y., Slevin M. A meta-analysis investigating the relationship between inflammation in autoimmune disease, elevated CRP, and the risk of dementia. Front. Immunol. 2023;14:1087571. doi: 10.3389/fimmu.2023.1087571. PubMed DOI PMC
Karabay E.A., Çerman A.A.; Altunay, İ.K. Evaluation of comorbidities in patients with autoimmune bullous diseases: A retrospective study. Sisli Etfal Hastan Tip Bul. 2018;52(4):302–306. PubMed PMC
Yeh F.C., Chen H.C., Chou Y.C., Lin C.L., Kao C.H., Lo H.Y., Liu F.C., Yang T.Y. Positive association of Parkinson’s disease with ankylosing spondylitis: A nationwide population-based study. J. Transl. Med. 2020;18(1):455. doi: 10.1186/s12967-020-02629-w. PubMed DOI PMC
Rønnow Sand J., Troelsen F.S., Horváth-Puhó E., Henderson V.W., Sørensen H.T., Erichsen R. Risk of dementia in patients with inflammatory bowel disease: A Danish population-based study. Aliment. Pharmacol. Ther. 2022;56(5):831–843. doi: 10.1111/apt.17119. PubMed DOI PMC
Zhang B., Wang H.E., Bai Y.M., Tsai S.J., Su T.P., Chen T.J., Wang Y.P., Chen M.H. Inflammatory bowel disease is associated with higher dementia risk: A nationwide longitudinal study. Gut. 2021;70(1):85–91. doi: 10.1136/gutjnl-2020-320789. PubMed DOI
Szandruk-Bender M., Wiatrak B.; Szeląg, A. The risk of developing Alzheimer’s disease and Parkinson’s disease in patients with inflammatory bowel disease: A meta-analysis. J. Clin. Med. 2022;11(13):3704. doi: 10.3390/jcm11133704. PubMed DOI PMC
Aggarwal M., Alkhayyat M., Abou Saleh M., Sarmini M.T., Singh A., Garg R., Garg P., Mansoor E., Padival R., Cohen B.L. Alzheimer disease occurs more frequently in patients with inflammatory bowel disease. J. Clin. Gastroenterol. 2023;57(5):501–507. doi: 10.1097/MCG.0000000000001714. PubMed DOI
Cui G., Li S., Ye H., Yang Y., Huang Q., Chu Y., Shi Z., Zhang X. Are neurodegenerative diseases associated with an increased risk of inflammatory bowel disease? A two-sample Mendelian randomization study. Front. Immunol. 2022;13:956005. doi: 10.3389/fimmu.2022.956005. PubMed DOI PMC
Li H., Wen Z. Effects of ulcerative colitis and Crohn’s disease on neurodegenerative diseases: A Mendelian randomization study. Front. Genet. 2022;13:846005. doi: 10.3389/fgene.2022.846005. PubMed DOI PMC
Freuer D., Meisinger C. Association between inflammatory bowel disease and Parkinson’s disease: A Mendelian randomization study. NPJ Parkinsons Dis. 2022;8(1):55. doi: 10.1038/s41531-022-00318-7. PubMed DOI PMC
Huang J., Su B., Karhunen V., Gill D., Zuber V., Ahola-Olli A., Palaniswamy S., Auvinen J., Herzig K.H., Keinänen-Kiukaanniemi S., Salmi M., Jalkanen S., Lehtimäki T., Salomaa V., Raitakari O.T., Matthews P.M., Elliott P., Tsilidis K.K., Jarvelin M., Tzoulaki I., Dehghan A. Inflammatory diseases, inflammatory biomarkers, and Alzheimer disease. Neurology. 2023;100(6):e568–e581. doi: 10.1212/WNL.0000000000201489. PubMed DOI PMC
Liu F.C., Huang W.Y., Lin T.Y., Shen C.H., Chou Y.C., Lin C.L., Lin K.T., Kao C.H. Inverse association of Parkinson disease with systemic lupus erythematosus. Medicine. 2015;94(46):e2097. doi: 10.1097/MD.0000000000002097. PubMed DOI PMC
Wang Y.C., Lin M.S., Huang A.P.H., Wu C.C., Kung W.M. Association between systemic rheumatic diseases and dementia risk: A meta-analysis. Front. Immunol. 2022;13:1054246. doi: 10.3389/fimmu.2022.1054246. PubMed DOI PMC
Jin T., Huang W., Cao F., Yu X., Guo S., Ying Z., Xu C. Causal association between systemic lupus erythematosus and the risk of dementia: A Mendelian randomization study. Front. Immunol. 2022;13:1063110. doi: 10.3389/fimmu.2022.1063110. PubMed DOI PMC
Chen H., Zhang S.M., Hernán M.A., Schwarzschild M.A., Willett W.C., Colditz G.A., Speizer F.E., Ascherio A. Nonsteroidal anti-inflammatory drugs and the risk of Parkinson disease. Arch. Neurol. 2003;60(8):1059–1064. doi: 10.1001/archneur.60.8.1059. PubMed DOI
Chen H., Jacobs E., Schwarzschild M.A., McCullough M.L., Calle E.E., Thun M.J., Ascherio A. Nonsteroidal antiinflammatory drug use and the risk for Parkinson’s disease. Ann. Neurol. 2005;58(6):963–967. doi: 10.1002/ana.20682. PubMed DOI
Gagne J.J., Power M.C. Anti-inflammatory drugs and risk of Parkinson disease: A meta-analysis. Neurology. 2010;74(12):995–1002. doi: 10.1212/WNL.0b013e3181d5a4a3. PubMed DOI PMC
Gao X., Chen H., Schwarzschild M.A., Ascherio A. Use of ibuprofen and risk of Parkinson disease. Neurology. 2011;76(10):863–869. doi: 10.1212/WNL.0b013e31820f2d79. PubMed DOI PMC
Powers K.M., Kay D.M., Factor S.A., Zabetian C.P., Higgins D.S., Samii A., Nutt J.G., Griffith A., Leis B., Roberts J.W., Martinez E.D., Montimurro J.S., Checkoway H., Payami H. Combined effects of smoking, coffee, and NSAIDs on Parkinson’s disease risk. Mov. Disord. 2008;23(1):88–95. doi: 10.1002/mds.21782. PubMed DOI
San Luciano M., Tanner C.M., Meng C., Marras C., Goldman S.M., Lang A.E., Tolosa E., Schüle B., Langston J.W., Brice A., Corvol J.C., Goldwurm S., Klein C., Brockman S., Berg D., Brockmann K., Ferreira J.J., Tazir M., Mellick G.D., Sue C.M., Hasegawa K., Tan E.K., Bressman S., Saunders-Pullman R., Saunders-Pullman R., Raymond D., Deik A., Barrett M.J., Cabassa J., Groves M., Hunt A.L., Lubarr N., Miravite J., Palmese C., Sachdev R., Sarva H., Severt L., Shanker V., Swan M.C., Soto-Valencia J., Johannes B., Ortega R., Ozelius L., Bressman S., Alcalay R.N., Tang M-X., Santana H.M., Roos E., Orbe-Reilly M., Fahn S., Cote L., Waters C., Mazzoni P., Ford B., Louis E., Levy O., Rosado L., Ruiz D., Dorovski T., Clark L., Marder K.S., Corvol J-C., Cormier F., Bonnet A-M., Welter M-L., Mesnage V., Vidailhet M., Roze E., Lacomblez L., Grabli D., Mart i Masso J.F., Martinez J.R., Mondragon R.E., Alustiza A.E., Pagola A.G., Pont-Sunyer C., Rolan D.V., Fernandez-Santiago R., Quintana M., Fernandez M., Maragall L., Hentati F., Farrer M., Duda J., Read M., Middleton L., Gibson R., Trinh J., Sassi S.B., Zouari M.; Rimamouri,; Farhat, E.; Nabli, F.; Aasly, J.; Warø, B.J.; Andersen, S.; Bertoni, J.; Carter, J.; Elmer, L.; Jimenez, N.G.; Martin, W.; Pahwa, R.; Lyons, K.; Reich, S.; Rodnitzky, R.; Ramos, C.S.; Wojcieszek, J.; Mirelman, A.; Gurevich, T.; Shira, A.B.; Weisz, M.G.; Yasinovsky, K.; Zalis, M.; Thaler, A.; Orr-Urtreger, A.; Giladi, N.; Mountain, J.; Mestre, T.; Visanji, N.; Ghate, T.; Singerman, J.; Al Dakheel, A.; Connolly, B.S.; Gasser, T.; Brockmann, K.; Conley, E.D.; Mullins, M.E.; Northover, C.; Facheris, M.; Fiske, B.; Urkowiz, A. Nonsteroidal anti-inflammatory use and LRRK2 Parkinson’s disease penetrance. Mov. Disord. 2020;35(10):1755–1764. doi: 10.1002/mds.28189. PubMed DOI PMC
Ren L., Yi J., Yang J., Li P., Cheng X., Mao P. Nonsteroidal anti-inflammatory drugs use and risk of Parkinson disease. Medicine. 2018;97(37):e12172. doi: 10.1097/MD.0000000000012172. PubMed DOI PMC
Brakedal B., Tzoulis C., Tysnes O.B., Haugarvoll K. NSAID use is not associated with Parkinson’s disease incidence: A Norwegian Prescription Database study. PLoS One. 2021;16(9):e0256602. doi: 10.1371/journal.pone.0256602. PubMed DOI PMC
Chou R.C., Kane M., Ghimire S., Gautam S., Gui J. Treatment for rheumatoid arthritis and risk of Alzheimer’s disease: A nested case/control analysis. CNS Drugs. 2016;30(11):1111–1120. doi: 10.1007/s40263-016-0374-z. PubMed DOI PMC
Zhou M., Xu R., Kaelber D.C., Gurney M.E. Tumor Necrosis Factor (TNF) blocking agents are associated with lower risk for Alzheimer’s disease in patients with rheumatoid arthritis and psoriasis. PLoS One. 2020;15(3):e0229819. doi: 10.1371/journal.pone.0229819. PubMed DOI PMC
Zheng C., Fillmore N.R., Ramos-Cejudo J., Brophy M., Osorio R., Gurney M.E., Qiu W.Q., Au R., Perry G., Dubreuil M., Chen S.G., Qi X., Davis P.B., Do N., Xu R. Potential long-term effect of tumor necrosis factor inhibitors on dementia risk: A propensity score matched retrospective cohort study in US veterans. Alzheimers Dement. 2022;18(6):1248–1259. doi: 10.1002/alz.12465. PubMed DOI PMC
Newby D., Prieto-Alhambra D., Duarte-Salles T., Ansell D., Pedersen L., van der Lei J., Mosseveld M., Rijnbeek P., James G., Alexander M., Egger P., Podhorna J., Stewart R., Perera G., Avillach P., Grosdidier S., Lovestone S., Nevado-Holgado A.J. Methotrexate and relative risk of dementia amongst patients with rheumatoid arthritis: A multi-national multi-database case-control study. Alzheimers Res. Ther. 2020;12(1):38. doi: 10.1186/s13195-020-00606-5. PubMed DOI PMC
Watad A., McGonagle D., Anis S., Carmeli R., Cohen A.D., Tsur A.M., Ben-Shabat N., Luigi Bragazzi N., Lidar M., Amital H. TNF inhibitors have a protective role in the risk of dementia in patients with ankylosing spondylitis: Results from a nationwide study. Pharmacol. Res. 2022;182:106325. doi: 10.1016/j.phrs.2022.106325. PubMed DOI
Peter I., Dubinsky M., Bressman S., Park A., Lu C., Chen N., Wang A. Anti–tumor necrosis factor therapy and incidence of Parkinson disease among patients with inflammatory bowel disease. JAMA Neurol. 2018;75(8):939–946. doi: 10.1001/jamaneurol.2018.0605. PubMed DOI PMC
Kern D.M., Lovestone S., Cepeda M.S. Treatment with TNF-α inhibitors versus methotrexate and the association with dementia and Alzheimer’s disease. Alzheimers Dement. 2021;7(1):e12163. doi: 10.1002/trc2.12163. PubMed DOI PMC
Desai R.J., Varma V.R., Gerhard T., Segal J., Mahesri M., Chin K., Horton D.B., Kim S.C., Schneeweiss S., Thambisetty M. Comparative risk of Alzheimer disease and related dementia among Medicare beneficiaries with Rheumatoid Arthritis treated with targeted disease/modifying antirheumatic agents. JAMA Netw. Open. 2022;5(4):e226567. doi: 10.1001/jamanetworkopen.2022.6567. PubMed DOI PMC
Fardet L., Nazareth I., Petersen I. Chronic hydroxychloroquine/chloroquine exposure for connective tissue diseases and risk of Alzheimer’s disease: A population-based cohort study. Ann. Rheum. Dis. 2019;78(2) doi: 10.1136/annrheumdis-2018-214016. , 279.2-282. PubMed DOI
Lai S.W., Kuo Y.H., Liao K.F. Chronic hydroxychloroquine exposure and the risk of Alzheimer’s disease. Ann. Rheum. Dis. 2021;80(7):e105. doi: 10.1136/annrheumdis-2019-216173. PubMed DOI
Varma V.R., Desai R.J., Navakkode S., Wong L.W., Anerillas C., Loeffler T., Schilcher I., Mahesri M., Chin K., Horton D.B., Kim S.C., Gerhard T., Segal J.B., Schneeweiss S., Gorospe M., Sajikumar S., Thambisetty M. Hydroxychloroquine lowers Alzheimer’s disease and related dementias risk and rescues molecular phenotypes related to Alzheimer’s disease. Mol. Psychiatry. 2023;28(3):1312–1326. doi: 10.1038/s41380-022-01912-0. PubMed DOI PMC
Mathieu S., Couderc M., Pereira B., Dubost J.J., Malochet-Guinamand S., Tournadre A., Soubrier M., Moisset X. Prevalence of migraine and neuropathic pain in rheumatic diseases. J. Clin. Med. 2020;9(6):1890. doi: 10.3390/jcm9061890. PubMed DOI PMC
Wu L., Xu Q., Zhou M., Chen Y., Jiang C., Jiang Y., Lin Y., He Q., Zhao L., Dong Y., Liu J., Chen W. Plasma miR-153 and miR-223 levels as potential biomarkers in Parkinson’s disease. Front. Neurosci. 2022;16:865139. doi: 10.3389/fnins.2022.865139. PubMed DOI PMC
Li D., Yang H., Ma J., Luo S., Chen S., Gu Q. MicroRNA-30e regulates neuroinflammation in MPTP model of Parkinson’s disease by targeting Nlrp3. Hum. Cell. 2018;31(2):106–115. doi: 10.1007/s13577-017-0187-5. PubMed DOI PMC
Taglialatela G., Rastellini C., Cicalese L. Reduced incidence of dementia in solid organ transplant patients treated with calcineurin inhibitors. J. Alzheimers Dis. 2015;47(2):329–333. doi: 10.3233/JAD-150065. PubMed DOI PMC
Bukhbinder A.S., Ling Y., Hasan O., Jiang X., Kim Y., Phelps K.N., Schmandt R.E., Amran A., Coburn R., Ramesh S., Xiao Q., Schulz P.E. Risk of Alzheimer’s disease following influenza vaccination: A claims-based cohort study using propensity score matching. J. Alzheimers Dis. 2022;88(3):1061–1074. doi: 10.3233/JAD-220361. PubMed DOI PMC
Klinger D., Hill B.L., Barda N., Halperin E., Gofrit O.N., Greenblatt C.L., Rappoport N., Linial M., Bercovier H. Bladder cancer immunotherapy by BCG is associated with a significantly reduced risk of Alzheimer’s disease and Parkinson’s disease. Vaccines, 2021;9(5):491. doi: 10.3390/vaccines9050491. PubMed DOI PMC
Al-kuraishy H.M., Al-Gareeb A.I., Saad H.M., Batiha G.E.S. Long-term use of metformin and Alzheimer’s disease: Beneficial or detrimental effects. Inflammopharmacology. 2023;31(3):1107–1115. doi: 10.1007/s10787-023-01163-7. PubMed DOI
McGeer P.L., Rogers J., McGeer E.G. Inflammation, anti-inflammatory agents and Alzheimer disease: The last 12 years. J. Alzheimers Dis. 2006;9(s3) Suppl.:271–276. doi: 10.3233/JAD-2006-9S330. PubMed DOI
Launer L.J. Nonsteroidal anti-inflammatory drug use and the risk for Alzheimer’s disease: dissecting the epidemiological evidence. Drugs. 2003;63(8):731–739. doi: 10.2165/00003495-200363080-00001. PubMed DOI
Daniels M.J.D., Rivers-Auty J., Schilling T., Spencer N.G., Watremez W., Fasolino V., Booth S.J., White C.S., Baldwin A.G., Freeman S., Wong R., Latta C., Yu S., Jackson J., Fischer N., Koziel V., Pillot T., Bagnall J., Allan S.M., Paszek P., Galea J., Harte M.K., Eder C., Lawrence C.B., Brough D. Fenamate NSAIDs inhibit the NLRP3 inflammasome and protect against Alzheimer’s disease in rodent models. Nat. Commun. 2016;7(1):12504. doi: 10.1038/ncomms12504. PubMed DOI PMC
Annadurai N., De Sanctis J.B., Hajdúch M., Das V. Tau secretion and propagation: Perspectives for potential preventive interventions in Alzheimer’s disease and other tauopathies. Exp. Neurol. 2021;343:113756. doi: 10.1016/j.expneurol.2021.113756. PubMed DOI
Annadurai N., Malina L., Malohlava J., Hajdúch M., Das V. Tau R2 and R3 are essential regions for tau aggregation, seeding and propagation. Biochimie. 2022;200:79–86. doi: 10.1016/j.biochi.2022.05.013. PubMed DOI
Annadurai N., Malina L., Salmona M., Diomede L., Bastone A., Cagnotto A., Romeo M., Šrejber M., Berka K., Otyepka M., Hajdúch M., Das V. Antitumour drugs targeting tau R3 VQIVYK and Cys322 prevent seeding of endogenous tau aggregates by exogenous seeds. FEBS J. 2022;289(7):1929–1949. doi: 10.1111/febs.16270. PubMed DOI
Annadurai N., Hrubý J.; Kubíčková, A.; Malina, L.; Hajdúch, M.; Das, V. Time- and dose-dependent seeding tendency of exogenous tau R2 and R3 aggregates in cells. Biochem. Biophys. Res. Commun. 2023;653:102–105. doi: 10.1016/j.bbrc.2023.02.057. PubMed DOI
Ferretti M.T., Allard S., Partridge V., Ducatenzeiler A., Cuello A.C. Minocycline corrects early, pre-plaque neuroinflammation and inhibits BACE-1 in a transgenic model of Alzheimer’s disease-like amyloid pathology. J. Neuroinflammation. 2012;9(1):62. doi: 10.1186/1742-2094-9-62. PubMed DOI PMC
Parashos S.A., Luo S., Biglan K.M., Bodis-Wollner I., He B., Liang G.S., Ross G.W., Tilley B.C., Shulman L.M. Measuring disease progression in early Parkinson disease. JAMA Neurol. 2014;71(6):710–716. doi: 10.1001/jamaneurol.2014.391. PubMed DOI PMC
Nassar N.N., Al-Shorbagy M.Y., Arab H.H., Abdallah D.M. Saxagliptin: A novel antiparkinsonian approach. Neuropharmacology. 2015;89:308–317. doi: 10.1016/j.neuropharm.2014.10.007. PubMed DOI
Chen S., Zhou M., Sun J., Guo A., Fernando R.L., Chen Y., Peng P., Zhao G., Deng Y. DPP-4 inhibitor improves learning and memory deficits and AD-like neurodegeneration by modulating the GLP-1 signaling. Neuropharmacology. 2019;157:107668. doi: 10.1016/j.neuropharm.2019.107668. PubMed DOI
Yu H., Sun T., He X., Wang Z., Zhao K., An J., Wen L., Li J.Y., Li W., Feng J. Association between Parkinson’s disease and diabetes mellitus: From epidemiology, pathophysiology and prevention to treatment. Aging Dis. 2022;13(6):1591–1605. doi: 10.14336/AD.2022.0325. PubMed DOI PMC
Landreth G., Jiang Q., Mandrekar S., Heneka M. PPARγ agonists as therapeutics for the treatment of Alzheimer’s disease. Neurotherapeutics. 2008;5(3):481–489. doi: 10.1016/j.nurt.2008.05.003. PubMed DOI PMC
Watson G.S., Cholerton B.A., Reger M.A., Baker L.D., Plymate S.R., Asthana S., Fishel M.A., Kulstad J.J., Green P.S., Cook D.G., Kahn S.E., Keeling M.L., Craft S. Preserved cognition in patients with early Alzheimer disease and amnestic mild cognitive impairment during treatment with rosiglitazone: A preliminary study. Am. J. Geriatr. Psychiatry. 2005;13(11):950–958. doi: 10.1176/appi.ajgp.13.11.950. PubMed DOI
Risner M.E., Saunders A.M., Altman J F B., Ormandy G.C., Craft S., Foley I.M., Zvartau-Hind M.E., Hosford D.A., Roses A.D. Efficacy of rosiglitazone in a genetically defined population with mild-to-moderate Alzheimer’s disease. Pharmacogenomics J. 2006;6(4):246–254. doi: 10.1038/sj.tpj.6500369. PubMed DOI
Alhowail A., Alsikhan R., Alsaud M., Aldubayan M., Rabbani S.I. Protective effects of pioglitazone on cognitive impairment and the underlying mechanisms: A review of literature. Drug Des. Devel. Ther. 2022;16:2919–2931. doi: 10.2147/DDDT.S367229. PubMed DOI PMC
Zhou Y., Chen Y., Xu C., Zhang H., Lin C. TLR4 targeting as a promising therapeutic strategy for Alzheimer disease treatment. Front. Neurosci. 2020;14:602508. doi: 10.3389/fnins.2020.602508. PubMed DOI PMC
Cui W., Sun C., Ma Y., Wang S., Wang X., Zhang Y. Inhibition of TLR4 Induces M2 microglial polarization and provides neuroprotection via the NLRP3 inflammasome in Alzheimer’s disease. Front. Neurosci. 2020;14:444. doi: 10.3389/fnins.2020.00444. PubMed DOI PMC
Jin X., Liu M.Y., Zhang D.F., Zhong X., Du K., Qian P., Yao W.F., Gao H., Wei M.J. Baicalin mitigates cognitive impairment and protects neurons from microglia-mediated neuroinflammation via suppressing NLRP 3 inflammasomes and TLR 4/NFκB signaling pathway. CNS Neurosci. Ther. 2019;25(5):575–590. doi: 10.1111/cns.13086. PubMed DOI PMC
Shi S., Liang D., Chen Y., Xie Y., Wang Y., Wang L., Wang Z., Qiao Z. Gx-50 reduces β-amyloid-induced TNF-α IL-1β NO, and PGE2 expression and inhibits NF-κB signaling in a mouse model of Alzheimer’s disease. Eur. J. Immunol. 2016;46(3):665–676. doi: 10.1002/eji.201545855. PubMed DOI
Kim C., Spencer B., Rockenstein E., Yamakado H., Mante M., Adame A., Fields J.A., Masliah D., Iba M., Lee H.J., Rissman R.A., Lee S.J., Masliah E. Immunotherapy targeting toll-like receptor 2 alleviates neurodegeneration in models of synucleinopathy by modulating α-synuclein transmission and neuroinflammation. Mol. Neurodegener. 2018;13(1):43. doi: 10.1186/s13024-018-0276-2. PubMed DOI PMC
Lee H., Jeon S.G., Kim J., Kang R.J., Kim S.M., Han K.M., Park H., Kim K., Sung Y.M., Nam H.Y., Koh Y.H., Song M., Suk K., Hoe H.S. Ibrutinib modulates Aβ/tau pathology, neuroinflammation, and cognitive function in mouse models of Alzheimer’s disease. Aging Cell. 2021;20(3):e13332. doi: 10.1111/acel.13332. PubMed DOI PMC
He P., Cheng X., Staufenbiel M., Li R., Shen Y. Long-term treatment of thalidomide ameliorates amyloid-like pathology through inhibition of β-secretase in a mouse model of Alzheimer’s disease. PLoS One. 2013;8(2):e55091. doi: 10.1371/journal.pone.0055091. PubMed DOI PMC
Decourt B., Drumm-Gurnee D., Wilson J., Jacobson S., Belden C., Sirrel S., Ahmadi M., Shill H., Powell J., Walker A., Gonzales A., Macias M., Sabbagh M.N. Poor safety and tolerability hamper reaching a potentially therapeutic dose in the use of thalidomide for Alzheimer’s disease: Results from a double-blind, placebo-controlled trial. Curr. Alzheimer Res. 2017;14(4):403–411. doi: 10.2174/1567205014666170117141330. PubMed DOI PMC
Decourt B., Wilson J., Ritter A., Dardis C., DiFilippo F., Zhuang X., Cordes D., Lee G., Fulkerson N., St Rose T., Hartley K., Sabbagh M. MCLENA-1: A phase ii clinical trial for the assessment of safety, tolerability, and efficacy of lenalidomide in patients with mild cognitive impairment due to Alzheimer’s disease. Open Access J. Clin. Trials. 2020;12:1–13. doi: 10.2147/OAJCT.S221914. PubMed DOI PMC
Palmas M.F., Ena A., Burgaletto C., Casu M.A., Cantarella G., Carboni E., Etzi M., De Simone A., Fusco G., Cardia M.C., Lai F., Picci L., Tweedie D., Scerba M.T., Coroneo V., Bernardini R., Greig N.H., Pisanu A., Carta A.R. Repurposing pomalidomide as a neuroprotective drug: Efficacy in an alpha-synuclein-based model of parkinson’s disease. Neurotherapeutics. 2022;19(1):305–324. doi: 10.1007/s13311-022-01182-2. PubMed DOI PMC
Singh S., Ganguly U., Pal S., Chandan G., Thakur R., Saini R.V., Chakrabarti S.S., Agrawal B.K., Chakrabarti S. Protective effects of cyclosporine A on neurodegeneration and motor impairment in rotenone-induced experimental models of Parkinson’s disease. Eur. J. Pharmacol. 2022;929:175129. doi: 10.1016/j.ejphar.2022.175129. PubMed DOI
Van der Perren A., Macchi F., Toelen J., Carlon M.S., Maris M., de Loor H., Kuypers D.R.J., Gijsbers R., Van den Haute C., Debyser Z., Baekelandt V. FK506 reduces neuroinflammation and dopaminergic neurodegeneration in an α-synuclein-based rat model for Parkinson’s disease. Neurobiol. Aging. 2015;36(3):1559–1568. doi: 10.1016/j.neurobiolaging.2015.01.014. PubMed DOI
Köylü A., Altunkaynak B.Z.; Delibaş, B. Effects of tacrolimus on c-fos in hippocampus and memory performances in streptozotocin model of Alzheimer’s disease of rats. Turk. J. Med. Sci. 2021;51(4):2159–2166. doi: 10.3906/sag-2008-291. PubMed DOI
Kumar A., Singh N. Calcineurin inhibition and protein kinase a activation limits cognitive dysfunction and histopathological damage in a model of dementia of the Alzheimer’s type. Curr. Neurovasc. Res. 2018;15(3):234–245. doi: 10.2174/1567202615666180813125125. PubMed DOI
Lai W.D., Wang S., You W.T., Chen S.J., Wen J.J., Yuan C.R., Zheng M.J., Jin Y., Yu J., Wen C.P. Sinomenine regulates immune cell subsets: Potential neuro-immune intervene for precise treatment of chronic pain. Front. Cell Dev. Biol. 2022;10:1041006. doi: 10.3389/fcell.2022.1041006. PubMed DOI PMC
Alam J., Blackburn K., Patrick D. Neflamapimod: Clinical phase 2b-ready oral small molecule inhibitor of p38α to reverse synaptic dysfunction in early Alzheimer’s disease. J. Prev. Alzheimers Dis. 2017;4(4):273–278. PubMed
Prins N.D., Harrison J.E., Chu H.M., Blackburn K., Alam J.J., Scheltens P. A phase 2 double-blind placebo-controlled 24-week treatment clinical study of the p38 alpha kinase inhibitor neflamapimod in mild Alzheimer’s disease. Alzheimers Res. Ther. 2021;13(1):106. doi: 10.1186/s13195-021-00843-2. PubMed DOI PMC
Rothhammer V., Kenison J.E., Li Z., Tjon E., Takenaka M.C., Chao C.C., Alves de Lima K., Borucki D.M., Kaye J., Quintana F.J. Aryl hydrocarbon receptor activation in astrocytes by laquinimod ameliorates autoimmune inflammation in the CNS. Neurol. Neuroimmunol. Neuroinflamm. 2021;8(2):e946. doi: 10.1212/NXI.0000000000000946. PubMed DOI PMC
Srivastava S., Rajopadhye R., Dey M., Singh R.K. Inhibition of MK2 kinase as a potential therapeutic target to control neuroinflammation in Alzheimer’s disease. Expert Opin. Ther. Targets. 2021;25(4):243–247. doi: 10.1080/14728222.2021.1924151. PubMed DOI
Roy S.M., Minasov G., Arancio O., Chico L.W., Van Eldik L.J., Anderson W.F., Pelletier J.C., Watterson D.M. A selective and brain penetrant p38αMAPK inhibitor candidate for neurologic and neuropsychiatric disorders that attenuates neuroinflammation and cognitive dysfunction. J. Med. Chem. 2019;62(11):5298–5311. doi: 10.1021/acs.jmedchem.9b00058. PubMed DOI PMC
Martínez G., Mijares M.R., De Sanctis J.B. Effects of flavonoids and its derivatives on immune cell responses. Recent Pat. Inflamm. Allergy Drug Discov. 2019;13(2):84–104. doi: 10.2174/1872213X13666190426164124. PubMed DOI
Ping Z., Xiaomu W., Xufang X., Liang S. Vinpocetine regulates levels of circulating TLRs in Parkinson’s disease patients. Neurol. Sci. 2019;40(1):113–120. doi: 10.1007/s10072-018-3592-y. PubMed DOI
Cui B., Guo X., You Y., Fu R. Farrerol attenuates MPP+induced inflammatory response by TLR4 signaling in a microglia cell line. Phytother. Res. 2019;33(4):1134–1141. doi: 10.1002/ptr.6307. PubMed DOI
Yang Y.L., Cheng X., Li W.H., Liu M., Wang Y.H., Du G.H. Kaempferol attenuates LPS-induced striatum injury in mice involving anti-neuroinflammation, maintaining BBB integrity, and down-regulating the HMGB1/TLR4 pathway. Int. J. Mol. Sci. 2019;20(3):491. doi: 10.3390/ijms20030491. PubMed DOI PMC
Yang L., Zhou R., Tong Y., Chen P., Shen Y., Miao S., Liu X. Neuroprotection by dihydrotestosterone in LPS-induced neuroinflammation. Neurobiol. Dis. 2020;140:104814. doi: 10.1016/j.nbd.2020.104814. PubMed DOI
Haddadi R., Nayebi A.M., Eyvari B.S. RETRACTED: Silymarin prevents apoptosis through inhibiting the Bax/caspase-3 expression and suppresses toll like receptor-4 pathway in the SNc of 6-OHDA intoxicated rats. Biomed. Pharmacother. 2018;104:127–136. doi: 10.1016/j.biopha.2018.05.020. PubMed DOI
Su Q., Ng W.L., Goh S.Y., Gulam M.Y., Wang L.F., Tan E.K., Ahn M., Chao Y.X. Targeting the inflammasome in Parkinson’s disease. Front. Aging Neurosci. 2022;14:957705. doi: 10.3389/fnagi.2022.957705. PubMed DOI PMC
Yang Y., Guo L., Wang J., Li W., Zhou X., Zhang C., Han C. Arglabin regulates microglia polarization to relieve neuroinflammation in Alzheimer’s disease. J. Biochem. Mol. Toxicol. 2022;36(6):e23045. doi: 10.1002/jbt.23045. PubMed DOI
Tong B.C.K., Huang A.S., Wu A.J., Iyaswamy A., Ho O.K.Y., Kong A.H.Y., Sreenivasmurthy S.G., Zhu Z., Su C., Liu J., Song J., Li M., Cheung K.H. Tetrandrine ameliorates cognitive deficits and mitigates tau aggregation in cell and animal models of tauopathies. J. Biomed. Sci. 2022;29(1):85. doi: 10.1186/s12929-022-00871-6. PubMed DOI PMC
Velagapudi R., Aderogba M., Olajide O.A. Tiliroside, a dietary glycosidic flavonoid, inhibits TRAF-6/NF-κB/p38-mediated neuroinflammation in activated BV2 microglia. Biochim. Biophys. Acta, Gen. Subj. 2014;1840(12):3311–3319. doi: 10.1016/j.bbagen.2014.08.008. PubMed DOI
Wu Q., Naeem A., Zou J., Yu C., Wang Y., Chen J., Ping Y. Isolation of phenolic compounds from raspberry based on molecular imprinting techniques and investigation of their anti-alzheimer’s disease properties. Molecules. 2022;27(20):6893. doi: 10.3390/molecules27206893. PubMed DOI PMC
Rezai-Zadeh K., Ehrhart J., Bai Y., Sanberg P.R., Bickford P., Tan J., Shytle R.D. Apigenin and luteolin modulate microglial activation via inhibition of STAT1-induced CD40 expression. J. Neuroinflammation. 2008;5(1):41. doi: 10.1186/1742-2094-5-41. PubMed DOI PMC
Liu R., Zhang T., Yang H., Lan X., Ying J., Du G. The flavonoid apigenin protects brain neurovascular coupling against amyloid-β₂₅₋₃₅-induced toxicity in mice. J. Alzheimers Dis. 2011;24(1):85–100. doi: 10.3233/JAD-2010-101593. PubMed DOI
Kang C.H., Choi Y.H., Moon S.K., Kim W.J., Kim G.Y. Quercetin inhibits lipopolysaccharide-induced nitric oxide production in BV2 microglial cells by suppressing the NF-κB pathway and activating the Nrf2-dependent HO-1 pathway. Int. Immunopharmacol. 2013;17(3):808–813. doi: 10.1016/j.intimp.2013.09.009. PubMed DOI
Wightman E.L., Haskell C.F., Forster J.S., Veasey R.C., Kennedy D.O. Epigallocatechin gallate, cerebral blood flow parameters, cognitive performance and mood in healthy humans: a double-blind, placebo-controlled, crossover investigation. Hum. Psychopharmacol. 2012;27(2):177–186. doi: 10.1002/hup.1263. PubMed DOI
Olajide O.A., Sarker S.D. Alzheimer’s disease: Natural products as inhibitors of neuroinflammation. Inflammopharmacology. 2020;28(6):1439–1455. doi: 10.1007/s10787-020-00751-1. PubMed DOI PMC
Moussa C., Hebron M., Huang X., Ahn J., Rissman R.A., Aisen P.S., Turner R.S. Resveratrol regulates neuro-inflammation and induces adaptive immunity in Alzheimer’s disease. J. Neuroinflammation. 2017;14(1):1. doi: 10.1186/s12974-016-0779-0. PubMed DOI PMC
Porro C., Cianciulli A., Trotta T., Lofrumento D.D., Panaro M.A. Curcumin regulates anti-inflammatory responses by JAK/STAT/SOCS signaling pathway in bv-2 microglial cells. Biology, 2019;8(3):51. doi: 10.3390/biology8030051. PubMed DOI PMC
Sorrenti V., Contarini G., Sut S., Dall’Acqua S., Confortin F., Pagetta A., Giusti P., Zusso M. Curcumin prevents acute neuroinflammation and long-term memory impairment induced by systemic lipopolysaccharide in mice. Front. Pharmacol. 2018;9:183. doi: 10.3389/fphar.2018.00183. PubMed DOI PMC
Sundaram J.R., Poore C.P., Sulaimee N.H.B., Pareek T., Cheong W.F., Wenk M.R., Pant H.C., Frautschy S.A., Low C.M., Kesavapany S. Curcumin ameliorates neuroinflammation, neurodegeneration, and memory deficits in p25 transgenic mouse model that bears hallmarks of alzheimer’s disease. J. Alzheimers Dis. 2017;60(4):1429–1442. doi: 10.3233/JAD-170093. PubMed DOI PMC
Ringman J.M., Frautschy S.A., Teng E., Begum A.N., Bardens J., Beigi M., Gylys K.H., Badmaev V., Heath D.D., Apostolova L.G., Porter V., Vanek Z., Marshall G.A., Hellemann G., Sugar C., Masterman D.L., Montine T.J., Cummings J.L., Cole G.M. Oral curcumin for Alzheimer’s disease: Tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study. Alzheimers Res. Ther. 2012;4(5):43. doi: 10.1186/alzrt146. PubMed DOI PMC
Cox K.H.M., Pipingas A., Scholey A.B. Investigation of the effects of solid lipid curcumin on cognition and mood in a healthy older population. J. Psychopharmacol. 2015;29(5):642–651. doi: 10.1177/0269881114552744. PubMed DOI
Small G.W., Siddarth P., Li Z., Miller K.J., Ercoli L., Emerson N.D., Martinez J., Wong K.P., Liu J., Merrill D.A., Chen S.T., Henning S.M., Satyamurthy N., Huang S.C., Heber D., Barrio J.R. Memory and brain amyloid and tau effects of a bioavailable form of curcumin in non-demented adults: A double-blind, placebo-controlled 18-month trial. Am. J. Geriatr. Psychiatry. 2018;26(3):266–277. doi: 10.1016/j.jagp.2017.10.010. PubMed DOI
Khare P., Datusalia A.K., Sharma S.S. Parthenolide, an NF-κB Inhibitor ameliorates diabetes-induced behavioural deficit, neurotransmitter imbalance and neuroinflammation in type 2 diabetes rat model. Neuromol. Med. 2017;19(1):101–112. doi: 10.1007/s12017-016-8434-6. PubMed DOI
Qiang W., Cai W., Yang Q., Yang L., Dai Y., Zhao Z., Yin J., Li Y., Li Q., Wang Y., Weng X., Zhang D., Chen Y., Zhu X., Artemisinin B., Artemisinin B. Improves learning and memory impairment in AD dementia mice by suppressing neuroinflammation. Neuroscience. 2018;395:1–12. doi: 10.1016/j.neuroscience.2018.10.041. PubMed DOI
Zhou J.M., Gu S.S., Mei W.H., Zhou J., Wang Z.Z., Xiao W. Ginkgolides and bilobalide protect BV2 microglia cells against OGD/reoxygenation injury by inhibiting TLR2/4 signaling pathways. Cell Stress Chaperones. 2016;21(6):1037–1053. doi: 10.1007/s12192-016-0728-y. PubMed DOI PMC
de Oliveira M.R. The dietary components carnosic acid and carnosol as neuroprotective agents: A Mechanistic View. Mol. Neurobiol. 2016;53(9):6155–6168. doi: 10.1007/s12035-015-9519-1. PubMed DOI
Velagapudi R., Kumar A., Bhatia H.S., El-Bakoush A., Lepiarz I., Fiebich B.L., Olajide O.A. Inhibition of neuroinflammation by thymoquinone requires activation of Nrf2/ARE signalling. Int. Immunopharmacol. 2017;48:17–29. doi: 10.1016/j.intimp.2017.04.018. PubMed DOI
Yang W., Qiu X., Wu Q., Chang F., Zhou T., Zhou M., Pei J. Active constituents of saffron (Crocus sativus L.) and their prospects in treating neurodegenerative diseases. (Review). Exp. Ther. Med. 2023;25(5):235. doi: 10.3892/etm.2023.11934. PubMed DOI PMC
Fu M., Liang X., Zhang X., Yang M., Ye Q., Qi Y., Liu H., Zhang X. Astaxanthin delays brain aging in senescence-accelerated mouse prone 10: inducing autophagy as a potential mechanism. Nutr. Neurosci. 2023;26(5):445–455. doi: 10.1080/1028415X.2022.2055376. PubMed DOI
Lin C.H., Chou C.C., Lee Y.H., Hung C.C. Curcumin facilitates aryl hydrocarbon receptor activation to ameliorate inflammatory astrogliosis. Molecules. 2022;27(8):2507. doi: 10.3390/molecules27082507. PubMed DOI PMC
Hong S., Beja-Glasser V.F., Nfonoyim B.M., Frouin A., Li S., Ramakrishnan S., Merry K.M., Shi Q., Rosenthal A., Barres B.A., Lemere C.A., Selkoe D.J., Stevens B. Complement and microglia mediate early synapse loss in Alzheimer mouse models. Science. 2016;352(6286):712–716. doi: 10.1126/science.aad8373. PubMed DOI PMC
Pittock S.J., Berthele A., Fujihara K., Kim H.J., Levy M., Palace J., Nakashima I., Terzi M., Totolyan N., Viswanathan S., Wang K.C., Pace A., Fujita K.P., Armstrong R., Wingerchuk D.M. Eculizumab in aquaporin-4-positive neuromyelitis optica spectrum disorder. N. Engl. J. Med. 2019;381(7):614–625. doi: 10.1056/NEJMoa1900866. PubMed DOI
Lamers C., Mastellos D.C., Ricklin D., Lambris J.D. Compstatins: The dawn of clinical C3-targeted complement inhibition. Trends Pharmacol. Sci. 2022;43(8):629–640. doi: 10.1016/j.tips.2022.01.004. PubMed DOI PMC
Lansita J.A., Mease K.M., Qiu H., Yednock T., Sankaranarayanan S., Kramer S. Nonclinical development of ANX005: A humanized anti-C1q antibody for treatment of autoimmune and neurodegenerative diseases. Int. J. Toxicol. 2017;36(6):449–462. doi: 10.1177/1091581817740873. PubMed DOI
Qi Y., Klyubin I., Cuello A.C., Rowan M.J. NLRP3-dependent synaptic plasticity deficit in an Alzheimer’s disease amyloidosis model in vivo. Neurobiol. Dis. 2018;114:24–30. doi: 10.1016/j.nbd.2018.02.016. PubMed DOI
Ben-Menachem-Zidon O., Ben-Menahem Y., Ben-Hur T., Yirmiya R. Intra-hippocampal transplantation of neural precursor cells with transgenic over-expression of IL-1 receptor antagonist rescues memory and neurogenesis impairments in an Alzheimer’s disease model. Neuropsychopharmacology. 2014;39(2):401–414. doi: 10.1038/npp.2013.208. PubMed DOI PMC
Cavanagh C., Tse Y.C., Nguyen H.B., Krantic S., Breitner J.C.S., Quirion R., Wong T.P. Inhibiting tumor necrosis factor-α before amyloidosis prevents synaptic deficits in an Alzheimer’s disease model. Neurobiol. Aging. 2016;47:41–49. doi: 10.1016/j.neurobiolaging.2016.07.009. PubMed DOI
Cavanagh C., Wong T.P. Preventing synaptic deficits in Alzheimer’s disease by inhibiting tumor necrosis factor alpha signaling. IBRO Rep. 2018;4:18–21. doi: 10.1016/j.ibror.2018.01.003. PubMed DOI PMC
Li Y., Fan H., Ni M., Zhang W., Fang F., Sun J., Lyu P., Ma P. Etanercept reduces neuron injury and neuroinflammation via inactivating c-Jun N-terminal kinase and nuclear factor-κB Pathways in Alzheimer’s disease: An in vitro and in vivo investigation. Neuroscience. 2022;484:140–150. doi: 10.1016/j.neuroscience.2021.11.001. PubMed DOI
Tobinick E., Gross H., Weinberger A., Cohen H. TNF-alpha modulation for treatment of Alzheimer’s disease: A 6-month pilot study. MedGenMed. 2006;8(2):25. PubMed PMC
Tobinick E.L., Gross H. Rapid improvement in verbal fluency and aphasia following perispinal etanercept in Alzheimer’s disease. BMC Neurol. 2008;8:27. doi: 10.1186/1471-2377-8-27. PubMed DOI PMC
Butchart J., Brook L., Hopkins V., Teeling J., Püntener U., Culliford D., Sharples R., Sharif S., McFarlane B., Raybould R., Thomas R., Passmore P., Perry V.H., Holmes C. Etanercept in Alzheimer disease: A randomized, placebo-controlled, double-blind, phase 2 trial. Neurology. 2015;84(21):2161–2168. doi: 10.1212/WNL.0000000000001617. PubMed DOI PMC
Tufan A.N., Holmes C., Tufan F. Etanercept in Alzheimer disease: A randomized, placebo-controlled, double-blind, phase 2 trialAuthor Response. Neurology. 2015;85(23) doi: 10.1212/01.wnl.0000475736.75775.25. , 2083.2-2084. PubMed DOI
Torres-Acosta N., O’Keefe J.H., O’Keefe E.L., Isaacson R., Small G. Therapeutic potential of TNF-α inhibition for Alzheimer’s disease prevention. J. Alzheimers Dis. 2020;78(2):619–626. doi: 10.3233/JAD-200711. PubMed DOI PMC
vom Berg J., Prokop S., Miller K.R., Obst J., Kälin R.E., Lopategui-Cabezas I., Wegner A., Mair F., Schipke C.G., Peters O., Winter Y., Becher B., Heppner F.L. Inhibition of IL-12/IL-23 signaling reduces Alzheimer’s disease-like pathology and cognitive decline. Nat. Med. 2012;18(12):1812–1819. doi: 10.1038/nm.2965. PubMed DOI
Pedrini S., Gupta V.B., Hone E., Doecke J., O’Bryant S., James I., Bush A.I., Rowe C.C., Villemagne V.L., Ames D., Masters C.L., Martins R.N., Savage G., Wilson B., Bourgeat P., Fripp J., Gibson S., Leroux H., McBride S., Salvado O., Fenech M., Francois M., Barnes M., Baker J., Barnham K., Bellingham S., Bomke J., Pejoska S.B., Buckley R., Cheng L., Collins S., Cooke I., Cyarto E., Darby D., Dore V., El-Sheikh D., Faux N., Fowler C., Harrington K., Hill A., Horne M., Jones G., Kamer A., Killeen N., Korrel H., Lamb F., Lautenschlager N., Lennon K., Li Q-X., Lim Y.Y., Louey A., Macaulay L., Mackintosh L., Maruff P., Mcilroy A., Nigro J., Perez K., Pertile K., Restrepo C., Cardoso B.R., Rembach A., Roberts B., Robertson J., Rumble R., Ryan T., Sach J., Silbert B., Thai C., Trounson B., Volitakis I., Vovos M., Ward L., Watt A., Williams R., Woodward M., Yates P., Ugarte F.Y., Zhang P., Bird S., Brown B., Burnham S., Chatterjee P., Cox K., Fernandez S., Fernando B., Gardener S., Laws S., Lim F., Lim L., Tegg M., Lucas K., Martins G., Porter T., Rainey-Smith S., Rodrigues M., Shen K.K., Sohrabi H., Taddei K., Taddei T., Tan S., Verdile G., Weinborn M., Farrow M., Frost S., Hanson D., Hor M., Kanagasingam Y., Leifert W., Lockett L., Riley M., Saunders I., Thomas P. A blood-based biomarker panel indicates IL-10 and IL-12/23p40 are jointly associated as predictors of β-amyloid load in an AD cohort. Sci. Rep. 2017;7(1):14057. doi: 10.1038/s41598-017-14020-9. PubMed DOI PMC
Eede P., Obst J., Benke E., Yvon-Durocher G., Richard B.C., Gimber N., Schmoranzer J., Böddrich A., Wanker E.E., Prokop S., Heppner F.L. Interleukin-/23 deficiency differentially affects pathology in male and female Alzheimer’s disease-like mice. EMBO Rep. 2020;21(3):e48530. doi: 10.15252/embr.201948530. PubMed DOI PMC
Porro C., Cianciulli A., Panaro M.A. The Regulatory Role of IL-10 in neurodegenerative diseases. Biomolecules. 2020;10(7):1017. doi: 10.3390/biom10071017. PubMed DOI PMC
Fei Z., Pan B., Pei R., Chen Z., Du X., Cao H., Li C. Efficacy and safety of blood derivatives therapy in Alzheimer’s disease: A systematic review and meta-analysis. Syst. Rev. 2022;11(1):256. doi: 10.1186/s13643-022-02115-y. PubMed DOI PMC
Rinne J.O., Brooks D.J., Rossor M.N., Fox N.C., Bullock R., Klunk W.E., Mathis C.A., Blennow K., Barakos J., Okello A.A. de LIano, S.R.M.; Liu, E.; Koller, M.; Gregg, K.M.; Schenk, D.; Black, R.; Grundman, M. 11C-PiB PET assessment of change in fibrillar amyloid-β load in patients with Alzheimer’s disease treated with bapineuzumab: A phase 2, double-blind, placebo-controlled, ascending-dose study. Lancet Neurol. 2010;9(4):363–372. doi: 10.1016/S1474-4422(10)70043-0. PubMed DOI
Vandenberghe R., Rinne J.O., Boada M., Katayama S., Scheltens P., Vellas B., Tuchman M., Gass A., Fiebach J.B., Hill D., Lobello K., Li D., McRae T., Lucas P., Evans I., Booth K., Luscan G., Wyman B.T., Hua L., Yang L., Brashear H.R., Black R.S. Bapineuzumab for mild to moderate Alzheimer’s disease in two global, randomized, phase 3 trials. Alzheimers Res. Ther. 2016;8(1):18. doi: 10.1186/s13195-016-0189-7. PubMed DOI PMC
Delnomdedieu M., Duvvuri S., Li D.J., Atassi N., Lu M., Brashear H.R., Liu E., Ness S., Kupiec J.W. First-In-Human safety and long-term exposure data for AAB-003 (PF-05236812) and biomarkers after intravenous infusions of escalating doses in patients with mild to moderate Alzheimer’s disease. Alzheimers Res. Ther. 2016;8(1):12. doi: 10.1186/s13195-016-0177-y. PubMed DOI PMC
Salloway S., Sperling R., Brashear H.R. Phase 3 trials of solanezumab and bapineuzumab for Alzheimer’s disease. N. Engl. J. Med. 2014;370(15):1460. PubMed
Salloway S., Sperling R., Fox N.C., Blennow K., Klunk W., Raskind M., Sabbagh M., Honig L.S., Porsteinsson A.P., Ferris S., Reichert M., Ketter N., Nejadnik B., Guenzler V., Miloslavsky M., Wang D., Lu Y., Lull J., Tudor I.C., Liu E., Grundman M., Yuen E., Black R., Brashear H.R.. Bapineuzumab 301 and 302 Clinical Trial Investigators. Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer’s disease. N. Engl. J. Med. 2014;370(4):322–333. doi: 10.1056/NEJMoa1304839. PubMed DOI PMC
Honig L.S., Vellas B., Woodward M., Boada M., Bullock R., Borrie M., Hager K., Andreasen N., Scarpini E., Liu-Seifert H., Case M., Dean R.A., Hake A., Sundell K., Poole Hoffmann V., Carlson C., Khanna R., Mintun M., DeMattos R., Selzler K.J., Siemers E. Trial of solanezumab for mild dementia due to alzheimer’s disease. N. Engl. J. Med. 2018;378(4):321–330. doi: 10.1056/NEJMoa1705971. PubMed DOI
Salloway S., Farlow M., McDade E., Clifford D.B., Wang G., Llibre-Guerra J.J., Hitchcock J.M., Mills S.L., Santacruz A.M., Aschenbrenner A.J., Hassenstab J., Benzinger T.L.S., Gordon B.A., Fagan A.M., Coalier K.A., Cruchaga C., Goate A.A., Perrin R.J., Xiong C., Li Y., Morris J.C., Snider B.J., Mummery C., Surti G.M., Hannequin D., Wallon D., Berman S.B., Lah J.J., Jimenez-Velazquez I.Z., Roberson E.D., van Dyck C.H., Honig L.S., Sánchez-Valle R., Brooks W.S., Gauthier S., Galasko D.R., Masters C.L., Brosch J.R., Hsiung G.Y.R., Jayadev S., Formaglio M., Masellis M., Clarnette R., Pariente J., Dubois B., Pasquier F., Jack C.R., Jr, Koeppe R., Snyder P.J., Aisen P.S., Thomas R.G., Berry S.M., Wendelberger B.A., Andersen S.W., Holdridge K.C., Mintun M.A., Yaari R., Sims J.R., Baudler M., Delmar P., Doody R.S., Fontoura P., Giacobino C., Kerchner G.A., Bateman R.J., Formaglio M., Mills S.L., Pariente J., van Dyck C.H. A trial of gantenerumab or solanezumab in dominantly inherited Alzheimer’s disease. Nat. Med. 2021;27(7):1187–1196. doi: 10.1038/s41591-021-01369-8. PubMed DOI PMC
Geerts H., Walker M., Rose R., Bergeler S., van der Graaf P.H., Schuck E., Koyama A., Yasuda S., Hussein Z., Reyderman L., Swanson C., Cabal A. A combined physiologically-based pharmacokinetic and quantitative systems pharmacology model for modeling amyloid aggregation in Alzheimer’s disease. CPT Pharmacometrics Syst. Pharmacol. 2023;12(4):444–461. doi: 10.1002/psp4.12912. PubMed DOI PMC
Hettmann T., Gillies S.D., Kleinschmidt M., Piechotta A., Makioka K., Lemere C.A., Schilling S., Rahfeld J.U., Lues I. Development of the clinical candidate PBD-C06, a humanized pGlu3-Aβ-specific antibody against Alzheimer’s disease with reduced complement activation. Sci. Rep. 2020;10(1):3294. doi: 10.1038/s41598-020-60319-5. PubMed DOI PMC
Mintun M.A., Lo A.C., Duggan Evans C., Wessels A.M., Ardayfio P.A., Andersen S.W., Shcherbinin S., Sparks J., Sims J.R., Brys M., Apostolova L.G., Salloway S.P., Skovronsky D.M. Donanemab in early Alzheimer’s disease. N. Engl. J. Med. 2021;384(18):1691–1704. doi: 10.1056/NEJMoa2100708. PubMed DOI
Lowe S.L., Duggan Evans C., Shcherbinin S., Cheng Y.J., Willis B.A., Gueorguieva I., Lo A.C., Fleisher A.S., Dage J.L., Ardayfio P., Aguiar G., Ishibai M., Takaichi G., Chua L., Mullins G., Sims J.R. Donanemab (LY3002813) Phase 1b study in alzheimer’s disease: Rapid and sustained reduction of brain amyloid measured by florbetapir F18 Imaging. J. Prev. Alzheimers Dis. 2021;8(4):414–424. PubMed
Gueorguieva I., Willis B.A., Chua L., Chow K., Ernest C.S., Shcherbinin S., Ardayfio P., Mullins G.R., Sims J.R. Donanemab population pharmacokinetics, amyloid plaque reduction, and safety in participants with Alzheimer’s disease. Clin. Pharmacol. Ther. 2023;113(6):1258–1267. doi: 10.1002/cpt.2875. PubMed DOI
Sevigny J., Chiao P., Bussière T., Weinreb P.H., Williams L., Maier M., Dunstan R., Salloway S., Chen T., Ling Y., O’Gorman J., Qian F., Arastu M., Li M., Chollate S., Brennan M.S., Quintero-Monzon O., Scannevin R.H., Arnold H.M., Engber T., Rhodes K., Ferrero J., Hang Y., Mikulskis A., Grimm J., Hock C., Nitsch R.M., Sandrock A. The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease. Nature. 2016;537(7618):50–56. doi: 10.1038/nature19323. PubMed DOI
Doroszkiewicz J., Mroczko B. New possibilities in the therapeutic approach to Alzheimer’s disease. Int. J. Mol. Sci. 2022;23(16):8902. doi: 10.3390/ijms23168902. PubMed DOI PMC
Söderberg L., Johannesson M., Nygren P., Laudon H., Eriksson F., Osswald G., Möller C., Lannfelt L. Lecanemab, aducanumab, and gantenerumab: Binding profiles to different forms of amyloid-beta might explain efficacy and side effects in clinical trials for alzheimer’s disease. Neurotherapeutics. 2023;20(1):195–206. doi: 10.1007/s13311-022-01308-6. PubMed DOI PMC
Brandt N.J., Wheeler C., Courtin S.O. Navigating disease-modifying treatments for Alzheimer’s disease: Focusing on medications in phase 3 clinical trials. J. Gerontol. Nurs. 2023;49(1):6–10. doi: 10.3928/00989134-20221205-02. PubMed DOI
Yuksel J.M., Noviasky J., Britton S. Aducanumab for Alzheimer’s disease: Summarized data from emerge, engage, and prime studies. Sr. Care Pharm. 2022;37(8):329–334. doi: 10.4140/TCP.n.2022.329. PubMed DOI
Swanson C.J., Zhang Y., Dhadda S., Wang J., Kaplow J., Lai R.Y.K., Lannfelt L., Bradley H., Rabe M., Koyama A., Reyderman L., Berry D.A., Berry S., Gordon R., Kramer L.D., Cummings J.L. A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer’s disease with lecanemab, an anti-Aβ protofibril antibody. Alzheimers Res. Ther. 2021;13(1):80. doi: 10.1186/s13195-021-00813-8. PubMed DOI PMC
Rafii M.S., Sperling R.A., Donohue M.C., Zhou J., Roberts C., Irizarry M.C., Dhadda S., Sethuraman G., Kramer L.D., Swanson C.J., Li D., Krause S., Rissman R.A., Walter S., Raman R., Johnson K.A., Aisen P.S. The AHEAD 3‐45 Study: Design of a prevention trial for Alzheimer’s disease. Alzheimers Dement. 2023;19(4):1227–1233. doi: 10.1002/alz.12748. PubMed DOI PMC
Knopman D.S. Lecanemab reduces brain amyloid-β and delays cognitive worsening. Cell Rep. Med. 2023;4(3):100982. doi: 10.1016/j.xcrm.2023.100982. PubMed DOI PMC
Piller C. Report on trial death stokes Alzheimer’s drug fears. Science. 2023;380(6641):122–123. doi: 10.1126/science.adi2242. PubMed DOI
Asuni A.A., Boutajangout A., Quartermain D., Sigurdsson E.M. Immunotherapy targeting pathological tau conformers in a tangle mouse model reduces brain pathology with associated functional improvements. J. Neurosci. 2007;27(34):9115–9129. doi: 10.1523/JNEUROSCI.2361-07.2007. PubMed DOI PMC
Boutajangout A., Ingadottir J., Davies P., Sigurdsson E.M. Passive immunization targeting pathological phospho-tau protein in a mouse model reduces functional decline and clears tau aggregates from the brain. J. Neurochem. 2011;118(4):658–667. doi: 10.1111/j.1471-4159.2011.07337.x. PubMed DOI PMC
Yanamandra K., Patel T.K., Jiang H., Schindler S., Ulrich J.D., Boxer A.L., Miller B.L., Kerwin D.R., Gallardo G., Stewart F., Finn M.B., Cairns N.J., Verghese P.B., Fogelman I., West T., Braunstein J., Robinson G., Keyser J., Roh J., Knapik S.S., Hu Y., Holtzman D.M., Holtzman D.M. Anti-tau antibody administration increases plasma tau in transgenic mice and patients with tauopathy. Sci. Transl. Med. 2017;9(386):eaal2029. doi: 10.1126/scitranslmed.aal2029. PubMed DOI PMC
Li L., Miao J., Jiang Y., Dai C.L., Iqbal K., Liu F., Chu D. Passive immunization inhibits tau phosphorylation and improves recognition learning and memory in 3xTg-AD mice. Exp. Neurol. 2023;362:114337. doi: 10.1016/j.expneurol.2023.114337. PubMed DOI
Novak P., Schmidt R., Kontsekova E., Zilka N., Kovacech B., Skrabana R., Vince-Kazmerova Z., Katina S., Fialova L., Prcina M., Parrak V., Dal-Bianco P., Brunner M., Staffen W., Rainer M., Ondrus M., Ropele S., Smisek M., Sivak R., Winblad B., Novak M. Safety and immunogenicity of the tau vaccine AADvac1 in patients with Alzheimer’s disease: A randomised, double-blind, placebo-controlled, phase 1 trial. Lancet Neurol. 2017;16(2):123–134. doi: 10.1016/S1474-4422(16)30331-3. PubMed DOI
Novak P., Zilka N., Zilkova M., Kovacech B., Skrabana R., Ondrus M., Fialova L., Kontsekova E., Otto M., Novak M. AADvac1, an active immunotherapy for Alzheimer’s disease and non alzheimer tauopathies: An overview of preclinical and clinical development. J. Prev. Alzheimers Dis. 2019;6(1):63–69. PubMed
Hovakimyan A., Zagorski K., Chailyan G., Antonyan T., Melikyan L., Petrushina I., Batt D.G., King O., Ghazaryan M., Donthi A., Foose C., Petrovsky N., Cribbs D.H., Agadjanyan M.G., Ghochikyan A. Immunogenicity of MultiTEP platform technology-based Tau vaccine in non-human primates. NPJ Vaccines. 2022;7(1):117. doi: 10.1038/s41541-022-00544-3. PubMed DOI PMC
Pagano G., Boess F.G., Taylor K.I., Ricci B., Mollenhauer B., Poewe W., Boulay A., Anzures-Cabrera J., Vogt A., Marchesi M., Post A., Nikolcheva T., Kinney G.G., Zago W.M., Ness D.K., Svoboda H., Britschgi M., Ostrowitzki S., Simuni T., Marek K., Koller M., Sevigny J., Doody R., Fontoura P., Umbricht D., Bonni A. A Phase II study to evaluate the safety and efficacy of prasinezumab in early parkinson’s disease (PASADENA): Rationale, design, and baseline data. Front. Neurol. 2021;12:705407. doi: 10.3389/fneur.2021.705407. PubMed DOI PMC
Pagano G., Taylor K.I., Anzures-Cabrera J., Marchesi M., Simuni T., Marek K., Postuma R.B., Pavese N., Stocchi F., Azulay J.P., Mollenhauer B., López-Manzanares L., Russell D.S., Boyd J.T., Nicholas A.P., Luquin M.R., Hauser R.A., Gasser T., Poewe W., Ricci B., Boulay A., Vogt A., Boess F.G., Dukart J., D’Urso G., Finch R., Zanigni S., Monnet A., Pross N., Hahn A., Svoboda H., Britschgi M., Lipsmeier F., Volkova-Volkmar E., Lindemann M., Dziadek S., Holiga Š., Rukina D., Kustermann T., Kerchner G.A., Fontoura P., Umbricht D., Doody R., Nikolcheva T., Bonni A. Trial of prasinezumab in early-stage parkinson’s disease. N. Engl. J. Med. 2022;387(5):421–432. doi: 10.1056/NEJMoa2202867. PubMed DOI
Kuchimanchi M., Monine M., Kandadi M.K., Woodward C., Penner N., Phase I.I. Phase II dose selection for alpha synuclein–targeting antibody cinpanemab (BIIB054) based on target protein binding levels in the brain. CPT Pharmacometrics Syst. Pharmacol. 2020;9(9):515–522. doi: 10.1002/psp4.12538. PubMed DOI PMC
Lang A.E., Siderowf A.D., Macklin E.A., Poewe W., Brooks D.J., Fernandez H.H., Rascol O., Giladi N., Stocchi F., Tanner C.M., Postuma R.B., Simon D.K., Tolosa E., Mollenhauer B., Cedarbaum J.M., Fraser K., Xiao J., Evans K.C., Graham D.L., Sapir I., Inra J., Hutchison R.M., Yang M., Fox T., Budd Haeberlein S., Dam T. Trial of cinpanemab in early parkinson’s disease. N. Engl. J. Med. 2022;387(5):408–420. doi: 10.1056/NEJMoa2203395. PubMed DOI
Schofield D.J., Irving L., Calo L., Bogstedt A., Rees G., Nuccitelli A., Narwal R., Petrone M., Roberts J., Brown L., Cusdin F., Dosanjh B., Lloyd C., Dobson C., Gurrell I., Fraser G., McFarlane M., Rockenstein E., Spencer B., Masliah E., Spillantini M.G., Tan K., Billinton A., Vaughan T., Chessell I., Perkinton M.S., Perkinton M.S. Preclinical development of a high affinity α-synuclein antibody, MEDI1341, that can enter the brain, sequester extracellular α-synuclein and attenuate α-synuclein spreading in vivo. Neurobiol. Dis. 2019;132:104582. doi: 10.1016/j.nbd.2019.104582. PubMed DOI
Fjord-Larsen L., Thougaard A., Wegener K.M., Christiansen J., Larsen F., Schrøder-Hansen L.M., Kaarde M., Ditlevsen D.K. Nonclinical safety evaluation, pharmacokinetics, and target engagement of Lu AF82422, a monoclonal IgG1 antibody against alpha-synuclein in development for treatment of synucleinopathies. MAbs. 2021;13(1):1994690. doi: 10.1080/19420862.2021.1994690. PubMed DOI PMC
Kallab M., Herrera-Vaquero M., Johannesson M., Eriksson F., Sigvardson J., Poewe W., Wenning G.K., Nordström E., Stefanova N. Region-specific effects of immunotherapy with antibodies targeting α-synuclein in a transgenic model of synucleinopathy. Front. Neurosci. 2018;12:452. doi: 10.3389/fnins.2018.00452. PubMed DOI PMC
Nordström E., Eriksson F., Sigvardson J., Johannesson M., Kasrayan A., Jones-Kostalla M., Appelkvist P., Söderberg L., Nygren P., Blom M., Rachalski A., Nordenankar K., Zachrisson O., Amandius E., Osswald G., Moge M., Ingelsson M., Bergström J., Lannfelt L., Möller C., Giorgetti M., Fälting J. ABBV-0805, a novel antibody selective for soluble aggregated α-synuclein, prolongs lifespan and prevents buildup of α-synuclein pathology in mouse models of Parkinson’s disease. Neurobiol. Dis. 2021;161:105543. doi: 10.1016/j.nbd.2021.105543. PubMed DOI
Gibbs E., Zhao B., Roman A., Plotkin S.S., Peng X., Hsueh S.C.C., Aina A., Wang J., Shyu C., Yip C.K., Nam S.E., Kaplan J.M., Cashman N.R. Rational generation of monoclonal antibodies selective for pathogenic forms of alpha-synuclein. Biomedicines. 2022;10(9):2168. doi: 10.3390/biomedicines10092168. PubMed DOI PMC
Valiukas Z., Ephraim R., Tangalakis K., Davidson M., Apostolopoulos V., Feehan J. Immunotherapies for Alzheimer’s disease: A review. Vaccines. 2022;10(9):1527. doi: 10.3390/vaccines10091527. PubMed DOI PMC
Knecht L., Folke J., Dodel R., Ross J.A., Albus A. Alpha-synuclein immunization strategies for synucleinopathies in clinical studies: A biological perspective. Neurotherapeutics. 2022;19(5):1489–1502. doi: 10.1007/s13311-022-01288-7. PubMed DOI PMC
Meissner W.G., Traon A.P.L., Foubert-Samier A., Galabova G., Galitzky M., Kutzelnigg A., Laurens B., Lührs P., Medori R., Péran P., Sabatini U., Vergnet S., Volc D., Poewe W., Schneeberger A., Staffler G., Rascol O., Anheim M., Castrioto A., Derkinderen P., Drapier S., Eusebio A., Grabli D., Marques A., Moreau C., Moro E., Tranchant C. A Phase 1 Randomized Trial of Specific Active α-SYNUCLEIN Immunotherapies PD01A and PD03A in Multiple System Atrophy. Mov. Disord. 2020;35(11):1957–1965. doi: 10.1002/mds.28218. PubMed DOI PMC
Yu H.J., Thijssen E., van Brummelen E., van der Plas J.L., Radanovic I., Moerland M., Hsieh E., Groeneveld G.J., Dodart J.C. A randomized first-in-human study with UB-312, a UBITh® α-synuclein peptide vaccine. Mov. Disord. 2022;37(7):1416–1424. doi: 10.1002/mds.29016. PubMed DOI PMC
Nimmo J.T., Smith H., Wang C.Y., Teeling J.L., Nicoll J.A.R., Verma A., Dodart J-C., Liu Z., Lin F., Carare R.O. Immunisation with UB-312 in the Thy1SNCA mouse prevents motor performance deficits and oligomeric α-synuclein accumulation in the brain and gut. Acta Neuropathol. 2022;143(1):55–73. doi: 10.1007/s00401-021-02381-5. PubMed DOI PMC
Schmidhuber S., Scheiblhofer S., Weiss R., Cserepes M., Tóvári J., Gadermaier G., Bezard E., De Giorgi F., Ichas F., Strunk D., Mandler M. A Novel C-type lectin receptor-targeted α-synuclein-based parkinson vaccine induces potent immune responses and therapeutic efficacy in mice. Vaccines. 2022;10(9):1432. doi: 10.3390/vaccines10091432. PubMed DOI PMC
Chen Z., Yang Y., Yang X., Zhou C., Li F., Lei P., Zhong L., Jin X., Peng G. Immune effects of optimized DNA vaccine and protective effects in a MPTP model of Parkinson’s disease. Neurol. Sci. 2013;34(9):1559–1570. doi: 10.1007/s10072-012-1284-6. PubMed DOI
Petrushina I., Hovakimyan A., Harahap-Carrillo I.S., Davtyan H., Antonyan T., Chailyan G., Kazarian K., Antonenko M., Jullienne A., Hamer M.M., Obenaus A., King O., Zagorski K., Blurton-Jones M., Cribbs D.H., Lander H., Ghochikyan A., Agadjanyan M.G. Characterization and preclinical evaluation of the cGMP grade DNA based vaccine, AV-1959D to enter the first-in-human clinical trials. Neurobiol. Dis. 2020;139:104823. doi: 10.1016/j.nbd.2020.104823. PubMed DOI PMC
Kim C., Hovakimyan A., Zagorski K., Antonyan T., Petrushina I., Davtyan H., Chailyan G., Hasselmann J., Iba M., Adame A., Rockenstein E., Szabo M., Blurton-Jones M., Cribbs D.H., Ghochikyan A., Masliah E., Agadjanyan M.G. Efficacy and immunogenicity of MultiTEP-based DNA vaccines targeting human α-synuclein: Prelude for IND enabling studies. NPJ Vaccines. 2022;7(1):1. doi: 10.1038/s41541-021-00424-2. PubMed DOI PMC
Masliah E., Rockenstein E., Mante M., Crews L., Spencer B., Adame A., Patrick C., Trejo M., Ubhi K., Rohn T.T., Mueller-Steiner S., Seubert P., Barbour R., McConlogue L., Buttini M., Games D., Schenk D. Passive immunization reduces behavioral and neuropathological deficits in an alpha-synuclein transgenic model of Lewy body disease. PLoS One. 2011;6(4):e19338. doi: 10.1371/journal.pone.0019338. PubMed DOI PMC
Nimmo J.T., Verma A., Dodart J.C., Wang C.Y., Savistchenko J., Melki R., Carare R.O., Nicoll J.A.R. Novel antibodies detect additional α-synuclein pathology in synucleinopathies: Potential development for immunotherapy. Alzheimers Res. Ther. 2020;12(1):159. doi: 10.1186/s13195-020-00727-x. PubMed DOI PMC
Games D., Valera E., Spencer B., Rockenstein E., Mante M., Adame A., Patrick C., Ubhi K., Nuber S., Sacayon P., Zago W., Seubert P., Barbour R., Schenk D., Masliah E. Reducing C-terminal-truncated alpha-synuclein by immunotherapy attenuates neurodegeneration and propagation in Parkinson’s disease-like models. J. Neurosci. 2014;34(28):9441–9454. doi: 10.1523/JNEUROSCI.5314-13.2014. PubMed DOI PMC
Wang S., Yu Y., Geng S., Wang D., Zhang L., Xie X., Wu B., Li C., Xu H., Li X., Hu Y., Zhang L., Kaether C., Wang B. A coimmunization vaccine of Aβ42 ameliorates cognitive deficits without brain inflammation in an Alzheimer’s disease model. Alzheimers Res. Ther. 2014;6(3):26. doi: 10.1186/alzrt256. PubMed DOI PMC
Xiao B., Tan E.K. Immunotherapy trials in parkinson’s disease: Challenges. J. Transl. Med. 2023;21(1):178. doi: 10.1186/s12967-023-04012-x. PubMed DOI PMC
Nicoll J.A.R., Buckland G.R., Harrison C.H., Page A., Harris S., Love S., Neal J.W., Holmes C., Boche D. Persistent neuropathological effects 14 years following amyloid-β immunization in Alzheimer’s disease. Brain. 2019;142(7):2113–2126. doi: 10.1093/brain/awz142. PubMed DOI PMC
Chu W.T., Hall J., Gurrala A., Becsey A., Raman S., Okun M.S., Flores C.T., Giasson B.I., Vaillancourt D.E., Vedam-Mai V. Evaluation of an adoptive cellular therapy-based vaccine in a transgenic mouse model of α-synucleinopathy. ACS Chem. Neurosci. 2023;14(2):235–245. doi: 10.1021/acschemneuro.2c00539. PubMed DOI PMC
Olson K.E., Namminga K.L., Schwab A.D., Thurston M.J., Lu Y., Woods A., Lei L., Shen W., Wang F., Joseph S.B., Gendelman H.E., Mosley R.L. Neuroprotective activities of long-acting granulocyte–macrophage colony-stimulating factor (mpdm608) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-intoxicated mice. Neurotherapeutics. 2020;17(4):1861–1877. doi: 10.1007/s13311-020-00877-8. PubMed DOI PMC
Olson K.E., Namminga K.L., Lu Y., Schwab A.D., Thurston M.J., Abdelmoaty M.M., Kumar V., Wojtkiewicz M., Obaro H., Santamaria P., Mosley R.L., Gendelman H.E. Safety, tolerability, and immune-biomarker profiling for year-long sargramostim treatment of Parkinson’s disease. EBioMedicine. 2021;67:103380. doi: 10.1016/j.ebiom.2021.103380. PubMed DOI PMC
Gendelman H.E., Zhang Y., Santamaria P., Olson K.E., Schutt C.R., Bhatti D., Shetty B.L.D., Lu Y., Estes K.A., Standaert D.G., Heinrichs-Graham E., Larson L., Meza J.L., Follett M., Forsberg E., Siuzdak G., Wilson T.W., Peterson C., Mosley R.L. Evaluation of the safety and immunomodulatory effects of sargramostim in a randomized, double-blind phase 1 clinical Parkinson’s disease trial. NPJ Parkinsons Dis. 2017;3(1):10. doi: 10.1038/s41531-017-0013-5. PubMed DOI PMC
Rohrer L., Yunce M., Montine T.J., Shan H. Plasma exchange in Alzheimer’s disease. Transfus. Med. Rev. 2023;37(1):10–15. PubMed
Boada M., López O.L., Olazarán J., Núñez L., Pfeffer M., Paricio M., Lorites J., Piñol-Ripoll G., Gámez J.E., Anaya F., Kiprov D., Lima J., Grifols C., Torres M., Costa M., Bozzo J., Szczepiorkowski Z.M., Hendrix S., Páez A. A randomized, controlled clinical trial of plasma exchange with albumin replacement for Alzheimer’s disease: Primary results of the AMBAR Study. Alzheimers Dement. 2020;16(10):1412–1425. doi: 10.1002/alz.12137. PubMed DOI PMC
Singh S., Kumar K., Panda M., Srivastava A., Mishra A., Prajapati V.K. High-throughput virtual screening of small-molecule inhibitors targeting immune cell checkpoints to discover new immunotherapeutics for human diseases. Mol. Divers. 2023;27(2):729–751. doi: 10.1007/s11030-022-10452-2. PubMed DOI
Liu Y., Meng Y., Zhou C., Yan J., Guo C., Dong W. Activation of the IL-17/TRAF6/NF-κB pathway is implicated in Aβ-induced neurotoxicity. BMC Neurosci. 2023;24(1):14. doi: 10.1186/s12868-023-00782-8. PubMed DOI PMC
Badr M., McFleder R.L., Wu J., Knorr S., Koprich J.B., Hünig T., Brotchie J.M., Volkmann J., Lutz M.B., Ip C.W. Expansion of regulatory T cells by CD28 superagonistic antibodies attenuates neurodegeneration in A53T-α-synuclein Parkinson’s disease mice. J. Neuroinflammation. 2022;19(1):319. doi: 10.1186/s12974-022-02685-7. PubMed DOI PMC