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Cerebrospinal fluid VILIP-1 and YKL-40, candidate biomarkers to diagnose, predict and monitor Alzheimer's disease in a memory clinic cohort.
Alzheimers Res Ther. 2015 Sep 17; 7(1):59.AR

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.

Links

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Authors+Show Affiliations

Kester MI
Alzheimer Center and Department of Neurology, VU University Medical Center, PO box 7057, 1007 MB, Amsterdam, The Netherlands. m.kester@vumc.nl.
Teunissen CE
Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands. c.teunissen@vumc.nl.
Sutphen C
The Knight Alzheimer's Disease Research Center, Washington University School of Medicine, 660 South Euclid, Campus Box 8111, St Louis, 63110, MO, USA. sutphenc@neuro.wustl.edu. Department of Neurology, Washington University School of Medicine, 660 South Euclid, Campus Box 8111, St Louis, 63110, MO, USA. sutphenc@neuro.wustl.edu. Hope Center for Neurological Disorders, Washington University School of Medicine, 660 South Euclid, Campus Box 8111, St Louis, 63110, MO, USA. sutphenc@neuro.wustl.edu.
Herries EM
Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid, Campus Box 8111, St Louis, 63110, MO, USA. e.herries@wustl.edu.
Ladenson JH
Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid, Campus Box 8111, St Louis, 63110, MO, USA. ladenson@wustl.edu.
Xiong C
The Knight Alzheimer's Disease Research Center, Washington University School of Medicine, 660 South Euclid, Campus Box 8111, St Louis, 63110, MO, USA. chengjie@wubios.wustl.edu. Division of Biostatistics, Washington University School of Medicine, 660 South Euclid, Campus Box 8111, St Louis, 63110, MO, USA. chengjie@wubios.wustl.edu.
Scheltens P
Alzheimer Center and Department of Neurology, VU University Medical Center, PO box 7057, 1007 MB, Amsterdam, The Netherlands. p.scheltens@vumc.nl.
van der Flier WM
Alzheimer Center and Department of Neurology, VU University Medical Center, PO box 7057, 1007 MB, Amsterdam, The Netherlands. wm.vdflier@vumc.nl. Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands. wm.vdflier@vumc.nl.
Morris JC
The Knight Alzheimer's Disease Research Center, Washington University School of Medicine, 660 South Euclid, Campus Box 8111, St Louis, 63110, MO, USA. morrisj@abraxas.wustl.edu. Department of Neurology, Washington University School of Medicine, 660 South Euclid, Campus Box 8111, St Louis, 63110, MO, USA. morrisj@abraxas.wustl.edu. Hope Center for Neurological Disorders, Washington University School of Medicine, 660 South Euclid, Campus Box 8111, St Louis, 63110, MO, USA. morrisj@abraxas.wustl.edu.
Holtzman DM
The Knight Alzheimer's Disease Research Center, Washington University School of Medicine, 660 South Euclid, Campus Box 8111, St Louis, 63110, MO, USA. holtzman@neuro.wustl.edu. Department of Neurology, Washington University School of Medicine, 660 South Euclid, Campus Box 8111, St Louis, 63110, MO, USA. holtzman@neuro.wustl.edu. Hope Center for Neurological Disorders, Washington University School of Medicine, 660 South Euclid, Campus Box 8111, St Louis, 63110, MO, USA. holtzman@neuro.wustl.edu.
Fagan AM
The Knight Alzheimer's Disease Research Center, Washington University School of Medicine, 660 South Euclid, Campus Box 8111, St Louis, 63110, MO, USA. fagana@neuro.wustl.edu. Department of Neurology, Washington University School of Medicine, 660 South Euclid, Campus Box 8111, St Louis, 63110, MO, USA. fagana@neuro.wustl.edu. Hope Center for Neurological Disorders, Washington University School of Medicine, 660 South Euclid, Campus Box 8111, St Louis, 63110, MO, USA. fagana@neuro.wustl.edu.

MeSH

AdipokinesAgedAlzheimer DiseaseAnalysis of VarianceBiomarkersChitinase-3-Like Protein 1Cognitive DysfunctionCross-Sectional StudiesDisease ProgressionFemaleFollow-Up StudiesHumansKaplan-Meier EstimateLectinsLinear ModelsLongitudinal StudiesMaleMiddle AgedNeurocalcinNeuropsychological TestsProportional Hazards ModelsSpinal Puncture

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26383836

Citation

Kester, Maartje I., et al. "Cerebrospinal Fluid VILIP-1 and YKL-40, Candidate Biomarkers to Diagnose, Predict and Monitor Alzheimer's Disease in a Memory Clinic Cohort." Alzheimer's Research & Therapy, vol. 7, no. 1, 2015, p. 59.
Kester MI, Teunissen CE, Sutphen C, et al. Cerebrospinal fluid VILIP-1 and YKL-40, candidate biomarkers to diagnose, predict and monitor Alzheimer's disease in a memory clinic cohort. Alzheimers Res Ther. 2015;7(1):59.
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. (2015). Cerebrospinal fluid VILIP-1 and YKL-40, candidate biomarkers to diagnose, predict and monitor Alzheimer's disease in a memory clinic cohort. Alzheimer's Research & Therapy, 7(1), 59. https://doi.org/10.1186/s13195-015-0142-1
Kester MI, et al. Cerebrospinal Fluid VILIP-1 and YKL-40, Candidate Biomarkers to Diagnose, Predict and Monitor Alzheimer's Disease in a Memory Clinic Cohort. Alzheimers Res Ther. 2015 Sep 17;7(1):59. PubMed PMID: 26383836.
* Article titles in AMA citation format should be in sentence-case
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, Y1 - 2015/09/17/ PY - 2015/02/05/received PY - 2015/08/14/accepted PY - 2015/9/19/entrez PY - 2015/9/19/pubmed PY - 2016/5/4/medline SP - 59 EP - 59 JF - Alzheimer's research & therapy JO - Alzheimers Res Ther VL - 7 IS - 1 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. SN - 1758-9193 UR - https://www.unboundmedicine.com/medline/citation/26383836/Cerebrospinal_fluid_VILIP_1_and_YKL_40_candidate_biomarkers_to_diagnose_predict_and_monitor_Alzheimer's_disease_in_a_memory_clinic_cohort_ DB - PRIME DP - Unbound Medicine ER -