TY - JOUR
T1 - Cerebrospinal fluid VILIP-1 and YKL-40, candidate biomarkers to diagnose, predict and monitor Alzheimer's disease in a memory clinic cohort
AU - Kester, Maartje I.
AU - Teunissen, Charlotte E.
AU - Sutphen, Courtney
AU - Herries, Elizabeth M.
AU - Ladenson, Jack H.
AU - Xiong, Chengjie
AU - Scheltens, Philip
AU - Van Der Flier, Wiesje M.
AU - Morris, John C.
AU - Holtzman, David M.
AU - Fagan, Anne M.
N1 - Funding Information:
Research of the VUmc Alzheimer Center is part of the Neurodegeneration Research Program of the Neuroscience Campus Amsterdam. The VUmc Alzheimer Center is supported by Alzheimer Nederland and Stichting VUmc funds. The clinical database structure was developed with funding from Stichting Dioraphte. Dr. M.I. Kester was financially supported by a research fellowship from Alzheimer Nederland (WE 15-2012-03). Assessment of YKL-40 and VILIP-1 was supported by a grant from Eli Lilly (DMH) and funding from Siemens Healthcare Diagnostics (JHL).
Funding Information:
CET serves as a member of the scientific advisory board of Innogenetics SA and Roche, received speaker honorarium on a Tea sponsored symposium, and received grants from the European Commission and the Alzheimer’s Drug Discovery Foundation. JHL is named on patents relating to VILIP-1; these patents and any possible licenses are being administered by Washington University in accordance with university policies. PS serves/has served on the advisory boards of Genentech, Novartis, Roche, Danone, Nutricia, Lilly, and Lund-beck; he has been a speaker at symposia organized by Lundbeck, Merz, Danone, Novartis, Roche, GE, and Genentech; for all his activities he receives no personal compensation. JCM reports no financial competing interests, neither he nor his family owns stock or has equity interest (outside of mutual funds or other externally directed accounts) in any pharmaceutical or biotechnology company; he has participated or is currently participating in clinical trials of antidementia drugs sponsored by Janssen Immunotherapy and Pfizer; he has served as a consultant for Lilly USA; and he receives research support from Eli Lilly/Avid Radiopharmaceuticals and is funded by NIH grants P50AG005681, P01AG003991, P01AG026276, and U19AG032438. DMH was supported by NIH grants P01-AG03991 and P01-AG026276 and a grant from Eli Lilly for the measurement of YKL-40. AMF serves on the scientific advisory boards of IBL International, Roche, and Novartis is a consultant for AbbVie. CS, EMH, CX, MIK, WMvdF declare that they have no competing interests.
Publisher Copyright:
© 2015 Kester et al.
PY - 2015/9/17
Y1 - 2015/9/17
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84941913037&partnerID=8YFLogxK
U2 - 10.1186/s13195-015-0142-1
DO - 10.1186/s13195-015-0142-1
M3 - Article
C2 - 26383836
AN - SCOPUS:84941913037
SN - 1758-9193
VL - 7
JO - Alzheimer's Research and Therapy
JF - Alzheimer's Research and Therapy
IS - 1
M1 - 59
ER -