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Cited by 146Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsCerebrospinal fluid and hydrocephalus

The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index.

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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Kester, Maartje I., Teunissen, Charlotte E., Sutphen, Courtney, Herries, Elizabeth M., Ladenson, Jack H., Xiong, Chengjie, Scheltens, Philip, van der Flier, Wiesje M., Morris, John C., Holtzman, David M., Fagan, Anne M.·2015·Alzheimer's Research & Therapy
DOI 10.1186/s13195-015-0142-1PMC PMC4574487
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Abstract

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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Crossref · 10.1186/s13195-015-0142-1

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Figures

Fig. 1 Kaplan–Meier curve for progression of MCI to AD. Progression of MCI to AD for tertiles of YKL-40 (upper) and VILIP-1 (lower). For YKL-40: lowest tertile, <219 ng/ml (light gray line); middle tertile, 219–328 ng/ml (dark gray line); and highest tertile, >328 ng/ml (black line). For VILIP-1: lowest tertile, <131 pg/ml (light gray line); middle tertile, 131–200 pg/ml (dark gray line); and highest tertile, >200 pg/ml (black line). Lowest tertile used as reference. AD Alzheimer’s disease, VILIP-1 Visinin-like protein-1, YKL-40 Chitinase-3-like protein 1
Fig. 1 Kaplan–Meier curve for progression of MCI to AD. Progression of MCI to AD for tertiles of YKL-40 (upper) and VILIP-1 (lower). For YKL-40: lowest tertile, <219 ng/ml (light gray line); middle tertile, 219–328 ng/ml (dark gray line); and highest tertile, >328 ng/ml (black line). For VILIP-1: lowest tertile, <131 pg/ml (light gray line); middle tertile, 131–200 pg/ml (dark gray line); and highest tertile, >200 pg/ml (black line). Lowest tertile used as reference. AD Alzheimer’s disease, VILIP-1 Visinin-like protein-1, YKL-40 Chitinase-3-like protein 1CC BY · PubMed Central
Fig. 2 Annual increase of CSF levels of YKL-40 and VILIP-1. Annual changes of CSF biomarker levels were assessed using age and sex-adjusted linear mixed models, with CSF biomarkers (VILIP-1 and YKL-40) as dependent variables and clinical diagnosis (categorical), time (LP interval in years), and interaction diagnosis × time as independent variables. The reported β value represents the estimated change of YKL-40 (ng/ml) or VILIP-1 (pg/ml) levels per year. Error bars represent SE of the reported effect. * p ≤0.005 for time effect, †p ≤0.05 for time effect. AD Alzheimer’s disease, MCI mild cognitive impairment, VILIP-1 Visinin-like protein-1, YKL-40 Chitinase-3-like protein 1
Fig. 2 Annual increase of CSF levels of YKL-40 and VILIP-1. Annual changes of CSF biomarker levels were assessed using age and sex-adjusted linear mixed models, with CSF biomarkers (VILIP-1 and YKL-40) as dependent variables and clinical diagnosis (categorical), time (LP interval in years), and interaction diagnosis × time as independent variables. The reported β value represents the estimated change of YKL-40 (ng/ml) or VILIP-1 (pg/ml) levels per year. Error bars represent SE of the reported effect. * p ≤0.005 for time effect, †p ≤0.05 for time effect. AD Alzheimer’s disease, MCI mild cognitive impairment, VILIP-1 Visinin-like protein-1, YKL-40 Chitinase-3-like protein 1CC BY · PubMed Central

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  1. Twisk JW. Applied longitudinal data analysis for epidemiology. Cambridge: Cambridge University Press; 2003.

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Metadata

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
Publisher
Springer Science and Business Media LLC
Published
2015-09-17
Volume
7
Issue
1
Pages
59-59
ISSN
1758-9193 (ISSN-L)
DOI
10.1186/s13195-015-0142-1
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
Licence
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
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Clinical Neurology › 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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