Cerebrospinal fluid phosphorylated tau,visinin-like protein-1,and chitinase-3-like protein 1 in mild cognitive impairment and Alzheimer’s disease

Hua Zhang; Kok Pin Ng; Joseph Therriault; Min Su Kang; Tharick APascoal; Pedro Rosa-Neto; Serge Gauthier; the Alzheimer’s Disease Neuroimaging Initiative

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Cerebrospinal fluid phosphorylated tau,visinin-like protein-1,and chitinase-3-like protein 1 in mild cognitive impairment and Alzheimer’s disease

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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 Aβstatus 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 Aβpathology across clinical stages of AD,while YKL-40 was correlated with Aβpathology 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.

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《转化神经变性病(英文)》 |2018年第1期|P.221-232|共12页
作者
Hua Zhang; Kok Pin Ng; Joseph Therriault; Min Su Kang; Tharick APascoal; Pedro Rosa-Neto; Serge Gauthier; the Alzheimer’s Disease Neuroimaging Initiative;
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Department of Neurology the First Affiliated Hospital of Chongqing Medical University Chongqing 400016 China;

Department of Neurology National Neuroscience Institute Singapore Singapore;

The McGill University Research Centre for Studies in Aging McGill University Montreal Canada;

The McGill University Research Centre for Studies in Aging McGill University Montreal Canada;

The McGill University Research Centre for Studies in Aging McGill University Montreal Canada;

The McGill University Research Centre for Studies in Aging McGill University Montreal Canada;

The McGill University Research Centre for Studies in Aging McGill University Montreal Canada;

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正文语种 chi
中图分类神经病学与精神病学;
关键词
Alzheimer’s; disease; Amyloid-β; Chitinase-3-like; protein; 1; Phosphorylated; tau; Visinin-like; protein-1;

Cerebrospinal fluid phosphorylated tau,visinin-like protein-1,and chitinase-3-like protein 1 in mild cognitive impairment and Alzheimer’s disease

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