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

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). We included 770 individuals with normal cognition, mild cognitive impairment, and Alzhei...

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Bibliographic Details
Published in:	Alzheimer's & dementia Vol. 15; no. 5; p. 644
Main Authors:	Bos, Isabelle, Vos, Stephanie, Verhey, Frans, Scheltens, Philip, Teunissen, Charlotte, Engelborghs, Sebastiaan, Sleegers, Kristel, Frisoni, Giovanni, Blin, Olivier, Richardson, Jill C, Bordet, Régis, Tsolaki, Magda, Popp, Julius, Peyratout, Gwendoline, Martinez-Lage, Pablo, Tainta, Mikel, Lleó, Alberto, Johannsen, Peter, Freund-Levi, Yvonne, Frölich, Lutz, Vandenberghe, Rik, Westwood, Sarah, Dobricic, Valerija, Barkhof, Frederik, Legido-Quigley, Cristina, Bertram, Lars, Lovestone, Simon, Streffer, Johannes, Andreasson, Ulf, Blennow, Kaj, Zetterberg, Henrik, Visser, Pieter Jelle
Format:	Journal Article
Language:	English
Published:	United States 01.05.2019
Subjects:	Aged Aged, 80 and over Alzheimer Disease - cerebrospinal fluid Alzheimer Disease - physiopathology Amyloid beta-Peptides Apolipoprotein E4 - genetics Biomarkers - cerebrospinal fluid Cognitive Dysfunction - cerebrospinal fluid Cognitive Dysfunction - physiopathology Female Humans Neurofilament Proteins - cerebrospinal fluid Neurogranin - cerebrospinal fluid tau Proteins - cerebrospinal fluid Neurogranin Neurofilament light Cognition APOE Amyloid-β Cerebrospinal fluid YKL-40 Alzheimer's disease
ISSN:	1552-5279, 1552-5279
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Summary:	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). 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. 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. Axonal degeneration, synaptic dysfunction, astroglial activation, and altered tau metabolism are involved already in preclinical AD. NFL may be a useful prognostic marker.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1552-5279 1552-5279
DOI:	10.1016/j.jalz.2019.01.004