Journal
ALZHEIMERS & DEMENTIA
Volume 15, Issue 5, Pages 644-654Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jalz.2019.01.004
Keywords
Alzheimer's disease; Amyloid-beta; Neurofilament light; Neurogranin; YKL-40; Cognition; Cerebrospinal fluid; APOE
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Funding
- Innovative Medicines Initiative Joint Undertaking under EMIF [115372]
- European Union's Seventh Framework Program (FP7/2007-2013)
- EFPIA companies
- European Commission [QLRT-2001-2455, 37,670]
- Department of Health of the Basque Government [17.0.1.08.12.0000.2.454.01.41142.001.H, 2016111096]
- Swiss National Research Foundation [SNF 320030_141179]
- University of Antwerp Research Fund, Belgium
- NIHR UCLH biomedical research center
- Department of Economic Promotion, Rural Areas and Territorial Balance of the Provincial Government of Gipuzkoa [124/16]
- Carlos III Institute of Health [PI15/00,919]
- Obra Social Kutxa-Fundazioa
- European Commission
- Dutch Research Council (ZonMW)
- Association of Frontotemporal Dementia/Alzheimer's Drug Discovery Foundation
- Alzheimer Netherlands
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Introduction: We investigated relations between amyloid-beta (A beta) status, apolipoprotein E (APOE) e4, 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 A beta status (Ab beta- vs. A beta+), clinical diagnosis APOE epsilon 4 carriership, baseline cognition, and change in cognition. Results: Ng and T-tau distinguished between A beta+ from A beta- individuals in each clinical group, whereas NFL and YKL-40 were associated with A beta+ in nondemented individuals only. APOE epsilon 4 carriership did not influence NFL, Ng, and YKL-40 in A beta+ individuals. NFL was the best predictor of cognitive decline in A beta+ 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. (C) 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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