Cerebrospinal fluid VILIP-1 and YKL-40, candidate biomarkers to diagnose, predict and monitor Alzheimer’s disease in a memory clinic cohort
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Introduction: We examined the utility of cerebrospinal fluid (CSF) proteins, Chitinase-3-like protein 1 (CHI3L1 or YKL-40), a putative marker of inflammation, and Visinin-like protein-1 (VILIP-1), a marker for neuronal injury, for diagnostic classification and monitoring of disease progression in a memory clinic cohort. Methods: CSF levels of YKL-40 and VILIP-1 were measured in 37 cognitively normal, 61 Mild Cognitive Impairment (MCI) and 65 Alzheimer’s disease (AD) patients from the memory clinic-based Amsterdam Dementia Cohort who underwent two lumbar punctures, with minimum interval of 6 months and a mean(SE) interval of 2.0(0.1) years. Mean(SE) cognitive follow-up was 3.8 (0.2) years. ANOVA was used to compare baseline differences of log-transformed CSF measures. Cox proportional hazard models were used to evaluate disease progression as a function of CSF tertiles. Linear mixed models were used to evaluate longitudinal change over time. All analyses were sex and age adjusted. Results: Baseline levels of YKL-40, but not VILIP-1, were higher in MCI and AD patients compared to cognitively normal individuals (mean (SE) pg/mL, 304 (16) and 288 (12) vs. 231 (16), p = 0.03 and p = 0.006). Baseline levels of both YKL-40 and VILIP-1 in MCI predicted progression to AD (HR 95 % CI = 3.0 (1.1–7.9) and 4.4 (1.5–13.0), respectively, for highest vs. lowest tertile). YKL-40 increased longitudinally in patients with MCI and AD (mean (SE) pg/mL per year, 8.9 (3.0) and 7.1 (3.1), respectively), but not in cognitively normal individuals, whereas levels of VILIP-1 increased only in MCI (mean (SE), 10.7 (2.6) pg/mL per year). Conclusions: CSF levels of YKL-40 may have utility for discriminating between cognitively normal individuals and patients with MCI or AD. Increased levels of both YKL-40 and VILIP-1 may be associated with disease progression. These CSF biomarkers should be considered for future evaluation in the characterization of the natural history of AD.
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Two earlier reports have found that YKL-40 predicted progression to AD.
“Two earlier reports have found that YKL-40 predicted progression to AD.22,49”
From CSF biomarkers of neuroinflammation and cerebrovascular dysfunction in early Alzheimer disease (2018) · cites this paper as [49]
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- Authors
- Kester, M. I., Teunissen, C. E., Sutphen, C., Herries, E. M., Ladenson, J. H., Xiong, C., Scheltens, P., van der Flier, W. M., Morris, J. C., Holtzman, D. M., & Fagan, A. M.
- Affiliations
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Washington University in St. Louis (US)
- Corresponding author
- Kester, Maartje I.
- ORCID
- Venue
- Alzheimer's Research & Therapy
- Published
- 2015-09-17
- Volume
- 7
- Issue
- 1
- Pages
- 59-59
- ISSN
- 1758-9193 (ISSN-L)
- PMC
- PMC4574487
- OpenAlex
- W1931861387
- Cited by
- 146
- References
- 53
- Citations by year
- 2026: 8 · 2025: 17 · 2024: 11 · 2023: 10 · 2022: 9 · 2021: 14 · 2020: 25 · 2019: 15 · 2018: 12 · 2017: 14 · 2016: 11
- FWCI
- 10.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Alzheimer s Research & Therapy (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Eli Lilly and Company
- Stichting Dioraphte
- Alzheimer Nederland
- National Institute on Aging (P50AG005681, P01AG003991, U19AG032438, P01AG026276)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Keywords
- Alzheimer's disease, VILIP-1, YKL-40, cerebrospinal fluid biomarkers, mild cognitive impairment, disease progression, neuroinflammation, neuronal injury, dementia diagnosis, longitudinal biomarker changes, memory clinic patients, cognitive decline prediction, disease surveillance
- MeSH terms
- Chitinase-3-Like Protein 1, Aged, Alzheimer Disease, Analysis of Variance, Cross-Sectional Studies, Female, Follow-Up Studies, Humans, Longitudinal Studies, Male, Middle Aged, Neuropsychological Tests, Spinal Puncture, Biomarkers, Linear Models, Proportional Hazards Models, Disease Progression, Lectins, Neurocalcin, Kaplan-Meier Estimate, Adipokines, Cognitive Dysfunction
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