TY - JOUR
T1 - Cerebrospinal fluid biomarkers of neurodegeneration, synaptic integrity, and astroglial activation across the clinical Alzheimer's disease spectrum
AU - Bos, Isabelle
AU - Vos, Stephanie
AU - Verhey, Frans
AU - Scheltens, Philip
AU - Teunissen, Charlotte
AU - Engelborghs, Sebastiaan
AU - Sleegers, Kristel
AU - Frisoni, Giovanni
AU - Blin, Olivier
AU - Richardson, Jill C.
AU - Bordet, Régis
AU - Tsolaki, Magda
AU - Popp, Julius
AU - Peyratout, Gwendoline
AU - Martinez-Lage, Pablo
AU - Tainta, Mikel
AU - Lleó, Alberto
AU - Johannsen, Peter
AU - Freund-Levi, Yvonne
AU - Frölich, Lutz
AU - Vandenberghe, Rik
AU - Westwood, Sarah
AU - Dobricic, Valerija
AU - Barkhof, Frederik
AU - Legido-Quigley, Cristina
AU - Bertram, Lars
AU - Lovestone, Simon
AU - Streffer, Johannes
AU - Andreasson, Ulf
AU - Blennow, Kaj
AU - Zetterberg, Henrik
AU - Visser, Pieter Jelle
PY - 2019/5/1
Y1 - 2019/5/1
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - Amyloid-β
KW - APOE
KW - Cerebrospinal fluid
KW - Cognition
KW - Neurofilament light
KW - Neurogranin
KW - YKL-40
UR - http://www.scopus.com/inward/record.url?scp=85062454355&partnerID=8YFLogxK
U2 - 10.1016/j.jalz.2019.01.004
DO - 10.1016/j.jalz.2019.01.004
M3 - Article
AN - SCOPUS:85062454355
SN - 1552-5260
VL - 15
SP - 644
EP - 654
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
IS - 5
ER -
