Cerebrospinal fluid biomarkers of neurodegeneration,synaptic integrity,and astroglial activation across the clinical Alzheimer's disease spectrum |
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| Institution: | 1. Universidad de los Andes, School of Medicine, Bogotá, Colombia;2. Universidad Militar Nueva Granada, School of Medicine, Bogotá, Colombia;3. Fundación Santa Fe de Bogotá, Section of Endocrinology, Bogotá, Colombia;1. Department of Neurology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China;2. Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou, Jiangsu, China. |
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| Abstract: | IntroductionWe investigated relations between amyloid-β (Aβ) status, apolipoprotein E (APOE) ε4, and cognition, with cerebrospinal fluid markers of neurogranin (Ng), neurofilament light (NFL), YKL-40, and total tau (T-tau).MethodsWe included 770 individuals with normal cognition, mild cognitive impairment, and Alzheimer's disease (AD)-type dementia from the EMIF-AD Multimodal Biomarker Discovery study. We tested the association of Ng, NFL, YKL-40, and T-tau with Aβ status (Aβ− vs. Aβ+), clinical diagnosis APOE ε4 carriership, baseline cognition, and change in cognition.ResultsNg and T-tau distinguished between Aβ+ from Aβ− individuals in each clinical group, whereas NFL and YKL-40 were associated with Aβ+ in nondemented individuals only. APOE ε4 carriership did not influence NFL, Ng, and YKL-40 in Aβ+ individuals. NFL was the best predictor of cognitive decline in Aβ+ individuals across the cognitive spectrum.DiscussionAxonal degeneration, synaptic dysfunction, astroglial activation, and altered tau metabolism are involved already in preclinical AD. NFL may be a useful prognostic marker. |
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| Keywords: | Alzheimer's disease Amyloid-β Neurofilament light Neurogranin YKL-40 Cognition Cerebrospinal fluid |
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