Bos, I;
Vos, S;
Verhey, F;
Scheltens, P;
Teunissen, C;
Engelborghs, S;
Sleegers, K;
... Visser, PJ; + view all
(2019)
Cerebrospinal fluid biomarkers of neurodegeneration, synaptic integrity, and astroglial activation across the clinical Alzheimer's disease spectrum.
Alzheimer's & Dementia
, 15
(5)
pp. 644-654.
10.1016/j.jalz.2019.01.004.
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Abstract
Introduction We 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). Methods We 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. Results Ng 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. Discussion Axonal 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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