Cerebrospinal fluid biomarkers of neurodegeneration, synaptic integrity, and astroglial activation across the clinical Alzheimer's disease spectrum

Journal article

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.

Authors: Bos, I; Vos, S; Verhey, F; Lovestone, S; Et al.

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Journal: Alzheimer's and Dementia
• Volume: 15
• Issue: 5
• Pages: 644-654
• Publication date: 2019-03-07
• Acceptance date: 2019-01-17
• DOI: 10.1016/j.jalz.2019.01.004
• ISSN: 1552-5260
• Language: English
• Keywords: cerebrospinal fluid; amyloid-beta; neurogranin; Alzheimer’s disease; YKL-40; APOE; cognition; neurofilament light