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Cerebrospinal fluid biomarkers of neurodegeneration, synaptic integrity, and astroglial activation across the clinical Alzheimer's disease spectrum
Author(s) -
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,
MartinezLage Pablo,
Tainta Mikel,
Lleó Alberto,
Johannsen Peter,
FreundLevi Yvonne,
Frölich Lutz,
Vandenberghe Rik,
Westwood Sarah,
Dobricic Valerija,
Barkhof Frederik,
LegidoQuigley Cristina,
Bertram Lars,
Lovestone Simon,
Streffer Johannes,
Andreasson Ulf,
Blennow Kaj,
Zetterberg Henrik,
Visser Pieter Jelle
Publication year - 2019
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2019.01.004
Subject(s) - neurodegeneration , apolipoprotein e , biomarker , dementia , cerebrospinal fluid , cognitive decline , neuroscience , cognition , psychology , disease , neurogranin , medicine , alzheimer's disease , oncology , biology , biochemistry , protein kinase c , enzyme
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.