Chitinase-3-Like 1 Protein (CHI3L1) Levels in Patients With Cognitive Deficits and Movement Disorders: Comparison With Other Biomarkers
Language English Country United States Media print
Document type Journal Article, Comparative Study
Grant support
reference number 340/2021
Ministerstvo Zdravotnictví Ceské Republiky
PubMed
40495463
PubMed Central
PMC12152271
DOI
10.1002/brb3.70619
Knihovny.cz E-resources
- Keywords
- Alzheimer's disease, CHI3L1, biomarkers, dementia,
- MeSH
- alpha-Synuclein cerebrospinal fluid blood MeSH
- Amyloid beta-Peptides blood cerebrospinal fluid MeSH
- Biomarkers blood cerebrospinal fluid MeSH
- Adult MeSH
- Cognitive Dysfunction * blood cerebrospinal fluid diagnosis MeSH
- Middle Aged MeSH
- Humans MeSH
- Neurofilament Proteins cerebrospinal fluid blood MeSH
- Movement Disorders * blood cerebrospinal fluid diagnosis MeSH
- Chitinase-3-Like Protein 1 * blood cerebrospinal fluid MeSH
- tau Proteins cerebrospinal fluid blood MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Comparative Study MeSH
- Names of Substances
- alpha-Synuclein MeSH
- Amyloid beta-Peptides MeSH
- Biomarkers MeSH
- CHI3L1 protein, human MeSH Browser
- neurofilament protein L MeSH Browser
- Neurofilament Proteins MeSH
- Chitinase-3-Like Protein 1 * MeSH
- tau Proteins MeSH
INTRODUCTION: Chitinase-3-like protein 1 (CHI3L1) is a glycoprotein implicated in various neurological conditions. It is associated with neuroinflammation and tissue remodeling. The study aimed to validate the reference interval (RI) of serum (S) CHI3L1 in a control group, to correlate S CHI3L1 values with other biomarkers of neurodegenerative damage, and to estimate the diagnostic accuracy of S CHI3L1. METHODS: Samples from 108 healthy volunteers were used to estimate the S CHI3L1 RI. For the comparison, we used cerebrospinal fluid (CSF) and serum (S) samples from 121 patients with cognitive disorders, and cognitive deterioration was assessed using the Mini-Mental State Examination (MMSE). ELISA assays were used to determine the S CHI3L1, CSF, and S neurofilament light chain (NfL) levels; CSF and plasma β-amyloid peptide42; CSF and plasma β-amyloid peptide40; CSF total tau protein; CSF phosphorylated tau protein; and CSF alpha-synuclein. RESULTS: The estimated RI of S CHI3L1 was 14.44 to 63.11 µg/L. The cut-off value of S CHI3L1 was 34.37 µg/L. ROC analysis showed that S CHI3L1 has 81.4% sensitivity and 76.9% specificity. We found a moderate Spearman's rank correlation coefficient between the S CHI3L1 and age (rS = 0.486; p < 0.001) and between S CHI3L1 and S NfL (rS = 0.489; p < 0.001) in all groups. The Kruskal-Wallis test showed a significant overall difference in S CHI3L1 among diagnostic groups (p = 0.013). S CHI3L1 and CSF NfL had statistically significant effects on MMSE values (multiple R2 was 0.431). CONCLUSIONS: Our results suggest that S CHI3L1 reflects the severity of cognitive deficits assessed by MMSE. It can be used as a supportive biomarker in neurodegenerative diseases.
Department of Clinical Neurosciences University of Ostrava Ostrava Czech Republic
Department of Neurology University Hospital Ostrava Ostrava Czech Republic
Institute of Laboratory Medicine University of Ostrava Ostrava Czech Republic
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Bara, I. , Ozier A., Girodet P.‐O., et al. 2012. “Role of YKL‐40 in Bronchial Smooth Muscle Remodeling in Asthma.” American Journal of Respiratory and Critical Care Medicine 185, no. 7: 715–722. 10.1164/rccm.201105-0915OC. PubMed DOI
Blennow, K. , and Zetterberg H.. 2018. “Biomarkers for Alzheimer's Disease: Current Status and Prospects for the Future.” Journal of Internal Medicine 284, no. 6: 643–663. 10.1111/joim.12816. PubMed DOI
Bonneh‐Barkay, D. , Bissel S. J., J. Kofler, A. Starkey, G. Wang,, and Wiley C. A.. 2012. “Astrocyte and Macrophage Regulation of YKL‐40 Expression and Cellular Response in Neuroinflammation.” Brain Pathology 22, no. 4: 530–546. 10.1111/j.1750-3639.2011.00550.x. PubMed DOI PMC
Bonneh‐Barkay, D. , G. Wang, A. Starkey, R. L. Hamilton,, and Wiley C. A.. 2010. “In Vivo CHI3L1 (YKL‐40) Expression in Astrocytes in Acute and Chronic Neurological Diseases.” Journal of Neuroinflammation 7, no. 1: 34. 10.1186/1742-2094-7-34. PubMed DOI PMC
Ciccocioppo, F. , G. Bologna, E. Ercolino, et al. 2020. “Neurodegenerative Diseases as Proteinopathies‐Driven Immune Disorders.” Neural Regeneration Research 15, no. 5: 850–856. 10.4103/1673-5374.268971. PubMed DOI PMC
Connolly, K. , M. Lehoux, R. O'Rourke, et al. 2023. “Potential Role of Chitinase‐3‐Like Protein 1 (CHI3L1/YKL‐40) in Neurodegeneration and Alzheimer's Disease.” Alzheimer's & Dementia 19, no. 1: 9–24. 10.1002/alz.12612. PubMed DOI PMC
Cubas‐Núñez, L. , S. Gil‐Perotín, J. Castillo‐Villalba, et al. 2021. “Potential Role of CHI3L1+ Astrocytes in Progression in MS.” Neurology, Neuroimmunology & Neuroinflammation 8, no. 3: e972. 10.1212/NXI.0000000000000972. PubMed DOI PMC
Dhiman, K. , V. B. Gupta, V. L. Villemagne, et al. 2020. “Cerebrospinal Fluid Neurofilament Light Concentration Predicts Brain Atrophy and Cognition in Alzheimer's Disease.” Alzheimer's & Dementia 12, no. 1: e12005. 10.1002/dad2.12005. PubMed DOI PMC
Dugger, B. N. , and Dickson D. W.. 2017. “Pathology of Neurodegenerative Diseases.” Cold Spring Harbor Perspectives in Biology 9, no. 7: a028035. 10.1101/cshperspect.a028035. PubMed DOI PMC
Ferri, C. P. , M. Prince, C. Brayne, et al. 2005. “Global Prevalence of Dementia: A Delphi Consensus Study.” Lancet 366, no. 9503: 2112–2117. 10.1016/S0140-6736(05)67889-0. PubMed DOI PMC
Haji, S. , Sako W., Murakami N., Osaki Y., and Izumi Y.. 2022. “Serum NfL and CHI3L1 for ALS and Parkinsonian Disorders in the Process of Diagnosis.” Journal of Neural Transmission 129, no. 3: 301–309. 10.1007/s00702-022-02470-z. PubMed DOI
Hampel, H. , N. Toschi, F. Baldacci, et al. 2018. “Alzheimer's Disease Biomarker‐Guided Diagnostic Workflow Using the Added Value of Six Combined Cerebrospinal Fluid Candidates: Aβ(1‐42), Total‐Tau, Phosphorylated‐Tau, NFL, Neurogranin, and YKL‐40.” Alzheimer's & Dementia 14, no. 4: 492–501. 10.1016/j.jalz.2017.11.015. PubMed DOI
Holper, S. , R. Watson,, and Yassi N.. 2022. “Tau as a Biomarker of Neurodegeneration.” International Journal of Molecular Sciences 23, no. 13: 7307. 10.3390/ijms23137307. PubMed DOI PMC
Hradilek, P. , K. Z. Revendova, J. Horakova, et al. 2023. “Cerebrospinal Fluid Neurofilament Light Chains and CXCL13 as Predictive Factors for Clinical Course of Multiple Sclerosis.” Biomedical Papers 167, no. 1: 30–35. 10.5507/bp.2023.002. PubMed DOI
Jack, C. R. J. , D. A. Bennett, K. Blennow, et al. 2018. “NIA‐AA Research Framework: Toward a Biological Definition of Alzheimer's Disease.” Alzheimer's & Dementia 14, no. 4: 535–562. 10.1016/j.jalz.2018.02.018. PubMed DOI PMC
Janelidze, S. , N. Mattsson, E. Stomrud, et al. 2018. “CSF Biomarkers of Neuroinflammation and Cerebrovascular Dysfunction in Early Alzheimer Disease.” Neurology 91, no. 9: e867–e877. 10.1212/WNL.0000000000006082. PubMed DOI PMC
Jiang, W. , F. Zhu, H. Xu, et al. 2023. “CHI3L1 Signaling Impairs Hippocampal Neurogenesis and Cognitive Function in Autoimmune‐Mediated Neuroinflammation.” Science Advances 9, no. 39: eadg8148. 10.1126/sciadv.adg8148. PubMed DOI PMC
Kravitz, B. A. , Corrada M. M., and Kawas C. H.. 2009. “Elevated C‐Reactive Protein Levels Are Associated With Prevalent Dementia in the Oldest‐Old.” Alzheimer's & Dementia 5, no. 4: 318–323. 10.1016/j.jalz.2009.04.1230. PubMed DOI PMC
Kušnierová, P. , D. Zeman, P. Hradílek, O. Zapletalová,, and Stejskal D.. 2020. “Determination of Chitinase 3‐Like 1 in Cerebrospinal Fluid in Multiple Sclerosis and Other Neurological Diseases.” PLoS One 15, no. 5: e0233519. 10.1371/journal.pone.0233519. PubMed DOI PMC
Lee, C. G. , da Silva C. A., Dela Cruz C. S., et al. 2011. “Role of Chitin and Chitinase/Chitinase‐Like Proteins in Inflammation, Tissue Remodeling, and Injury.” Annual Review of Physiology 73: 479–501. 10.1146/annurev-physiol-012110-142250. PubMed DOI PMC
Muszyński, P. , M. Groblewska, A. Kulczyńska‐Przybik, A. Kułakowska,, and Mroczko B.. 2017. “YKL‐40 as a Potential Biomarker and a Possible Target in Therapeutic Strategies of Alzheimer's Disease.” Current Neuropharmacology 15, no. 6: 906–917. 10.2174/1570159x15666170208124324. PubMed DOI PMC
Ng, A. , W. W. Tam, M. W. Zhang, et al. 2018. “IL‐1β, IL‐6, TNF‐α and CRP in Elderly Patients With Depression or Alzheimer's Disease: Systematic Review and Meta‐Analysis.” Scientific Reports 8, no. 1: 12050. 10.1038/s41598-018-30487-6. PubMed DOI PMC
Nichols, E. , C. E. Szoeke, S. Vollser, et al. 2019. “Global, Regional, and National Burden of Alzheimer's Disease and Other Dementias, 1990–2016: A Systematic Analysis for the Global Burden of Disease Study 2016.” Lancet Neurology 18, no. 1: 88–106. 10.1016/S1474-4422(18)30403-4. PubMed DOI PMC
Ning, L. , and Wang B.. 2022. “Neurofilament Light Chain in Blood as a Diagnostic and Predictive Biomarker for Multiple Sclerosis: A Systematic Review and Meta‐Analysis.” PLoS One 17, no. 9: e0274565. 10.1371/journal.pone.0274565. PubMed DOI PMC
Novobilský, R. , P. Bartova, K. Lichá, M. Bar, D. Stejskal,, and Kusnierova P.. 2023. “Serum Neurofilament Light Chain Levels in Patients With Cognitive Deficits and Movement Disorders: Comparison of Cerebrospinal and Serum Neurofilament Light Chain Levels With Other Biomarkers.” Frontiers in Human Neuroscience 17: 1284416. 10.3389/fnhum.2023.1284416. PubMed DOI PMC
Pase, M. P. , J. J. Himali, R. Puerta, et al. 2024. “Association of Plasma YKL‐40 with MRI, CSF, and Cognitive Markers of Brain Health and Dementia.” Neurology 102, no. 4: e208075. 10.1212/WNL.0000000000208075. PubMed DOI PMC
Postuma, R. B. , D. Berg, M. Stern, et al. 2015. “MDS Clinical Diagnostic Criteria for Parkinson's Disease.” Movement Disorders 30, no. 12: 1591–1601. 10.1002/mds.26424. PubMed DOI
Rehli, M. , S. W. Krause,, and Andreesen R.. 1997. “Molecular Characterization of the Gene for Human Cartilage Gp‐39 (CHI3L1), a Member of the Chitinase Protein family and Marker for Late Stages of Macrophage Differentiation.” Genomics 43, no. 2: 221–225. 10.1006/geno.1997.4778. PubMed DOI
Robinson, J. L. , S. X. Xie, D. R. Baer, et al. 2023. “Pathological Combinations in Neurodegenerative Disease Are Heterogeneous and Disease‐associated.” Brain 146, no. 6: 2557–2569. 10.1093/brain/awad059. PubMed DOI PMC
Sanfilippo, C. , P. Castrogiovanni, R. Imbesi, et al. 2019. “Sex Difference in CHI3L1 Expression Levels in Human Brain Aging and in Alzheimer's Disease.” Brain Research 1720: 146305. 10.1016/j.brainres.2019.146305. PubMed DOI
Sanfilippo, C. , Malaguarnera L., and Di Rosa M.. 2016. “Chitinase Expression in Alzheimer's Disease and Non‐Demented Brains Regions.” Journal of the Neurological Sciences 369: 242–249. 10.1016/j.jns.2016.08.029. PubMed DOI
Schneider, R. , B. Bellenberg, B. Gisevius, et al. 2021. “Chitinase 3‐Like 1 and Neurofilament Light Chain in CSF and CNS Atrophy in MS.” Neurology, Neuroimmunology & Neuroinflammation 8, no. 1: e906. 10.1212/NXI.0000000000000906. PubMed DOI PMC
Sutherland, T. E. 2018. “Chitinase‐Like Proteins as Regulators of Innate Immunity and Tissue Repair: Helpful Lessons for Asthma?” Biochemical Society Transactions 46, no. 1: 141–151. 10.1042/BST20170108. PubMed DOI
Yu, J. E. , I. J. Yeo, S.‐B. Han, et al. 2024. “Significance of Chitinase‐3‐Like Protein 1 in the Pathogenesis of Inflammatory Diseases and Cancer.” Experimental & Molecular Medicine 56, no. 1: 1–18. 10.1038/s12276-023-01131-9. PubMed DOI PMC
Zhao, T. , Z. Su, Y. Li, X. Zhang,, and You Q.. 2020. “Chitinase‐3 Like‐Protein‐1 Function and Its Role in Diseases.” Signal Transduction and Targeted Therapy 5, no. 1: 201. 10.1038/s41392-020-00303-7. PubMed DOI PMC
Zheng, H. , Q. Chen, J. Zhang, et al. 2023. “Postoperative Serum CHI3L1 Level Is Associated With Postoperative Cognitive Dysfunction in Elderly Patients After Hip Fracture Surgery: A Prospective Observational Study.” Heliyon 9, no. 8: e18796. 10.1016/j.heliyon.2023.e18796. PubMed DOI PMC