Alzheimer's disease (AD) is an irreversible, incurable, progressive neurodegenerative illness, where dementia symptoms gradually worsen over a number of years. The research of validated biomarkers for AD is essential to improve diagnosis and accelerate the development of new therapies. Biochemical markers including neuroimaging could facilitate diagnosis, predict AD progression from a pre-AD state of mild cognitive impairment, and be used to detect the efficacies of disease-modifying therapies. Established biomarkers of AD from cerebrospinal fluid and neuroimaging are highly accurate, but barriers to clinical implementation exist. The focus on blood-based AD biomarkers has grown exponentially during the past few decades. An ideal diagnostic test for AD should be noninvasive and easily applicable. Clinical cost-effectiveness also needs to be established.

1st Faculty of Medicine Charles University Prague Prague Czech Republic

Department of Psychiatry General University Hospital Prague Prague Czech Republic

Zobrazit více v PubMed

Galasko D. Expanding the repertoire of biomarkers for Alzheimer’s disease: targeted and non-targeted approaches. Front Neurol. 2015;6:256. PubMed PMC

WUSTL Washington University of St. Luis. [Accessed May 11, 2017]. Available from: http://neuroscienceresearch.wustl.edu/News.aspx.

Alzheimer’s Association A future without Alzheimer’s; 2017. [Accessed May, 2017]. Available from: http://www.alz.org/research/overview.asp.

Zetterberg H. Applying fluid biomarkers to Alzheimer’s disease. Am J Physiol Cell Physiol. 2017;313(1):C3–C10. PubMed PMC

World Health Organization . International Alzheimer’s Disease. Dementia: a public health priority. WHO; p. 2012. Available from: http://www.who.int/mental_health/publications/dementia_report_2012.

Hurd MD, Martorell P, Delavande A, Mullen KJ, Langa KM. Monetary costs of dementia in the United States. N Engl J Med. 2013;368(14):1326–1334. PubMed PMC

Fiandaca MS, Zhong X, Cheema AK, et al. Plasma 24-metabolite panel predicts preclinical transition to clinical stages of Alzheimer’s disease. Front Neurol. 2015;6:237. PubMed PMC

O’Bryant SE, Mielke MM, Rissman RA, et al. Blood-based biomarkers in Alzheimer disease: current state of the science and a novel collaborative paradigm for advancing from discovery to clinic. Alzheimers Dement. 2017;13(1):45–58. PubMed PMC

Panegyres PK, Chen HY. Differences between early and late onset Alzheimer’s disease. Am J Neurodegener Dis. 2013;2(4):300–306. PubMed PMC

Chintamaneni M, Bhaskar M. Biomarkers in Alzheimer’s disease: a review. ISRN Pharmacol. 2012;2012:984786–6. PubMed PMC

Dubois B, Feldman HH, Jacova C, et al. Research criteria for the diagnosis of Alzheimer’s disease: revising the NINCDS-ADRDA criteria. Lancet Neurol. 2007;6(8):734–746. PubMed

Carswell CJ, Win Z, Muckle K, et al. Clinical utility of amyloid PET imaging with (18)F-florbetapir: a retrospective study of 100 patients. J Neurol Neurosurg Psychiatry. 2018;89(3):294–299. PubMed

Rabinovici GD, Rosen HJ, Alkalay A, et al. Amyloid vs FDG-PET in the differential diagnosis of AD and FTLD. Neurology. 2011;77(23):2034–2042. PubMed PMC

Su Y, Blazey TM, Owen CJ, et al. Correction: quantitative amyloid imaging in autosomal dominant Alzheimer’s disease: results from the DIAN study group. PLoS One. 2016;11(9):e0163669. PubMed PMC

Morris JK, Honea RA, Vidoni ED, Swerdlow RH, Burns JM. Is Alzheimer’s disease a systemic disease? Biochim Biophys Acta. 2014;1842(9):1340–1349. PubMed PMC

Wurtman R. Biomarkers in the diagnosis and management of Alzheimer’s disease. Metabolism. 2015;64(3 Suppl 1):S47–S50. PubMed

Selkoe DJ, Hardy J. The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol Med. 2016;8(6):595–608. PubMed PMC

Takahashi RH, Nagao T, Gouras GK. Plaque formation and the intraneuronal accumulation of β-amyloid in Alzheimer’s disease. Pathol Int. 2017;67(4):185–193. PubMed

Pláteník J, Fišar Z, Buchal R, et al. GSK3β, CREB, and BDNF in peripheral blood of patients with Alzheimer’s disease and depression. Prog Neuropsychopharmacol Biol Psychiatry. 2014;50:83–93. PubMed

Martins-de-Souza D. Biomarkers for psychiatric disorders: where are we standing? Dis Markers. 2013;35(1):1–2. PubMed PMC

Maes OC, Schipper HM, Chertkow HM, Wang E. Methodology for discovery of Alzheimer’s disease blood-based biomarkers. J Gerontol A Biol Sci Med Sci. 2009;64(6):636–645. PubMed

Blennow K. A review of fluid biomarkers for Alzheimer’s disease: moving from CSF to blood. Neurol Ther. 2017;6(Suppl 1):15–24. PubMed PMC

Lewczuk P, Riederer P, O’Bryant SE, et al. Cerebrospinal fluid and blood biomarkers for neurodegenerative dementias: an update of the consensus of the task force on biological markers in psychiatry of the world federation of societies of biological psychiatry. World J Biol Psychiatry. 2018;19(4):244–328. PubMed PMC

Khan TK, Alkon DL. Peripheral biomarkers of Alzheimer’s disease. J Alzheimers Dis. 2015;44(3):729–744. PubMed

Humpel C. Identifying and validating biomarkers for Alzheimer’s disease. Trends Biotechnol. 2011;29(1):26–32. PubMed PMC

Kvartsberg H, Duits FH, Ingelsson M, et al. Cerebrospinal fluid levels of the synaptic protein neurogranin correlates with cognitive decline in prodromal Alzheimer’s disease. Alzheimers Dement. 2015;11(10):1180–1190. PubMed

Folch J, Petrov D, Ettcheto M, et al. Current research therapeutic strategies for Alzheimer’s disease treatment. Neural Plast. 2016;2016:1–15. PubMed PMC

Heneka MT, Carson MJ, El Khoury J, et al. Neuroinflammation in Alzheimer’s disease. Lancet Neurol. 2015;14(4):388–405. PubMed PMC

Voyle N, Baker D, Burnham SC, et al. Blood protein markers of neocortical amyloid-β burden: a candidate study using SOMAscan technology. J Alzheimers Dis. 2015;46(4):947–961. PubMed PMC

Huynh RA, Mohan C. Alzheimer’s disease: biomarkers in the genome, blood, and cerebrospinal fluid. Front Neurol. 2017;8:102. PubMed PMC

Nicolas G, Wallon D, Charbonnier C, et al. Screening of dementia genes by whole-exome sequencing in early-onset Alzheimer disease: input and lessons. Eur J Hum Genet. 2016;24(5):710–716. PubMed PMC

Foo JN, Liu JJ, Tan EK. Whole-genome and whole-exome sequencing in neurological diseases. Nat Rev Neurol. 2012;8(9):508–517. PubMed

Mattsson N, Zetterberg H, Janelidze S, et al. Plasma tau in Alzheimer disease. Neurology. 2016;87(17):1827–1835. PubMed PMC

Mattsson N, Andreasson U, Zetterberg H, Blennow K. Alzheimer’s disease neuroimaging I. Association of plasma neurofilament light with neurodegeneration in patients with Alzheimer disease. JAMA Neurol. 2017;74:557–566. PubMed PMC