Cargando…
Cerebrospinal fluid phosphorylated tau, visinin-like protein-1, and chitinase-3-like protein 1 in mild cognitive impairment and Alzheimer’s disease
BACKGROUND: Visinin-like protein-1 (VILIP-1) and chitinase-3-like protein 1 (CHI3L1 or YKL-40) in cerebrospinal fluid (CSF) are newly discovered markers indicating neuronal damage and microglial activation, respectively. Phosphorylated tau (p-tau) reflects the neuropathology of Alzheimer’s disease (...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6161434/ https://www.ncbi.nlm.nih.gov/pubmed/30311914 http://dx.doi.org/10.1186/s40035-018-0127-7 |
_version_ | 1783358987397234688 |
---|---|
author | Zhang, Hua Ng, Kok Pin Therriault, Joseph Kang, Min Su Pascoal, Tharick A. Rosa-Neto, Pedro Gauthier, Serge |
author_facet | Zhang, Hua Ng, Kok Pin Therriault, Joseph Kang, Min Su Pascoal, Tharick A. Rosa-Neto, Pedro Gauthier, Serge |
author_sort | Zhang, Hua |
collection | PubMed |
description | BACKGROUND: Visinin-like protein-1 (VILIP-1) and chitinase-3-like protein 1 (CHI3L1 or YKL-40) in cerebrospinal fluid (CSF) are newly discovered markers indicating neuronal damage and microglial activation, respectively. Phosphorylated tau (p-tau) reflects the neuropathology of Alzheimer’s disease (AD) and is useful as diagnostic markers for AD. However, it is unknown whether these biomarkers have similar or complementary information in AD. METHODS: We stratified 121 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database into cognitively normal (CN), stable mild cognitive impairment (sMCI), progressive MCI (pMCI), and dementia due to AD. Analysis of covariance (ANOVA) and chi-square analyses, Spearman correlation, and logistic regression models were performed to test the demographic, associations between biomarkers, and diagnostic accuracies, respectively. Linear mixed-effects models were used to evaluate the effects of CSF amyloid-β (Aβ) on above biomarkers within diagnostic groups, the combination of diagnostic group and Aβ status as predictor, and CSF biomarkers as predictors of AD features, including cognition measured by Mini–Mental State Examination (MMSE) and brain structure and white matter hyperintensity (WMH) measured by magnetic resonance imaging (MRI). RESULTS: P-tau, VILIP-1, and YKL-40 were all predictors of AD diagnosis, but combinations of biomarkers did not improve the diagnostic accuracy (AUC 0.924 for p-tau, VILIP-1, and YKL-40) compared to p-tau (AUC 0.922). P-tau and VILIP-1 were highly correlated (r = 0.639, p < 0.001) and strongly associated with Aβ pathology across clinical stages of AD, while YKL-40 was correlated with Aβ pathology in CN and AD groups. VILIP-1 was associated with acceleration of cognitive decline, hippocampal atrophy, and expansion of ventricles in longitudinal analyses. YKL-40 was associated with hippocampal atrophy at baseline and follow-up, while p-tau was only associated with worsening WMH at baseline. CONCLUSIONS: CSF levels of p-tau, VILIP-1, and YKL-40 may have utility for discriminating between cognitively normal subjects and patients with AD. Increased levels of both VILIP-1 and YKL-40 may be associated with disease degeneration. These CSF biomarkers should be considered for future assessment in the characterization of the natural history of AD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40035-018-0127-7) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6161434 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-61614342018-10-01 Cerebrospinal fluid phosphorylated tau, visinin-like protein-1, and chitinase-3-like protein 1 in mild cognitive impairment and Alzheimer’s disease Zhang, Hua Ng, Kok Pin Therriault, Joseph Kang, Min Su Pascoal, Tharick A. Rosa-Neto, Pedro Gauthier, Serge Transl Neurodegener Research BACKGROUND: Visinin-like protein-1 (VILIP-1) and chitinase-3-like protein 1 (CHI3L1 or YKL-40) in cerebrospinal fluid (CSF) are newly discovered markers indicating neuronal damage and microglial activation, respectively. Phosphorylated tau (p-tau) reflects the neuropathology of Alzheimer’s disease (AD) and is useful as diagnostic markers for AD. However, it is unknown whether these biomarkers have similar or complementary information in AD. METHODS: We stratified 121 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database into cognitively normal (CN), stable mild cognitive impairment (sMCI), progressive MCI (pMCI), and dementia due to AD. Analysis of covariance (ANOVA) and chi-square analyses, Spearman correlation, and logistic regression models were performed to test the demographic, associations between biomarkers, and diagnostic accuracies, respectively. Linear mixed-effects models were used to evaluate the effects of CSF amyloid-β (Aβ) on above biomarkers within diagnostic groups, the combination of diagnostic group and Aβ status as predictor, and CSF biomarkers as predictors of AD features, including cognition measured by Mini–Mental State Examination (MMSE) and brain structure and white matter hyperintensity (WMH) measured by magnetic resonance imaging (MRI). RESULTS: P-tau, VILIP-1, and YKL-40 were all predictors of AD diagnosis, but combinations of biomarkers did not improve the diagnostic accuracy (AUC 0.924 for p-tau, VILIP-1, and YKL-40) compared to p-tau (AUC 0.922). P-tau and VILIP-1 were highly correlated (r = 0.639, p < 0.001) and strongly associated with Aβ pathology across clinical stages of AD, while YKL-40 was correlated with Aβ pathology in CN and AD groups. VILIP-1 was associated with acceleration of cognitive decline, hippocampal atrophy, and expansion of ventricles in longitudinal analyses. YKL-40 was associated with hippocampal atrophy at baseline and follow-up, while p-tau was only associated with worsening WMH at baseline. CONCLUSIONS: CSF levels of p-tau, VILIP-1, and YKL-40 may have utility for discriminating between cognitively normal subjects and patients with AD. Increased levels of both VILIP-1 and YKL-40 may be associated with disease degeneration. These CSF biomarkers should be considered for future assessment in the characterization of the natural history of AD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40035-018-0127-7) contains supplementary material, which is available to authorized users. BioMed Central 2018-09-10 /pmc/articles/PMC6161434/ /pubmed/30311914 http://dx.doi.org/10.1186/s40035-018-0127-7 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Zhang, Hua Ng, Kok Pin Therriault, Joseph Kang, Min Su Pascoal, Tharick A. Rosa-Neto, Pedro Gauthier, Serge Cerebrospinal fluid phosphorylated tau, visinin-like protein-1, and chitinase-3-like protein 1 in mild cognitive impairment and Alzheimer’s disease |
title | Cerebrospinal fluid phosphorylated tau, visinin-like protein-1, and chitinase-3-like protein 1 in mild cognitive impairment and Alzheimer’s disease |
title_full | Cerebrospinal fluid phosphorylated tau, visinin-like protein-1, and chitinase-3-like protein 1 in mild cognitive impairment and Alzheimer’s disease |
title_fullStr | Cerebrospinal fluid phosphorylated tau, visinin-like protein-1, and chitinase-3-like protein 1 in mild cognitive impairment and Alzheimer’s disease |
title_full_unstemmed | Cerebrospinal fluid phosphorylated tau, visinin-like protein-1, and chitinase-3-like protein 1 in mild cognitive impairment and Alzheimer’s disease |
title_short | Cerebrospinal fluid phosphorylated tau, visinin-like protein-1, and chitinase-3-like protein 1 in mild cognitive impairment and Alzheimer’s disease |
title_sort | cerebrospinal fluid phosphorylated tau, visinin-like protein-1, and chitinase-3-like protein 1 in mild cognitive impairment and alzheimer’s disease |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6161434/ https://www.ncbi.nlm.nih.gov/pubmed/30311914 http://dx.doi.org/10.1186/s40035-018-0127-7 |
work_keys_str_mv | AT zhanghua cerebrospinalfluidphosphorylatedtauvisininlikeprotein1andchitinase3likeprotein1inmildcognitiveimpairmentandalzheimersdisease AT ngkokpin cerebrospinalfluidphosphorylatedtauvisininlikeprotein1andchitinase3likeprotein1inmildcognitiveimpairmentandalzheimersdisease AT therriaultjoseph cerebrospinalfluidphosphorylatedtauvisininlikeprotein1andchitinase3likeprotein1inmildcognitiveimpairmentandalzheimersdisease AT kangminsu cerebrospinalfluidphosphorylatedtauvisininlikeprotein1andchitinase3likeprotein1inmildcognitiveimpairmentandalzheimersdisease AT pascoaltharicka cerebrospinalfluidphosphorylatedtauvisininlikeprotein1andchitinase3likeprotein1inmildcognitiveimpairmentandalzheimersdisease AT rosanetopedro cerebrospinalfluidphosphorylatedtauvisininlikeprotein1andchitinase3likeprotein1inmildcognitiveimpairmentandalzheimersdisease AT gauthierserge cerebrospinalfluidphosphorylatedtauvisininlikeprotein1andchitinase3likeprotein1inmildcognitiveimpairmentandalzheimersdisease AT cerebrospinalfluidphosphorylatedtauvisininlikeprotein1andchitinase3likeprotein1inmildcognitiveimpairmentandalzheimersdisease |