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
N1 - Funding Information:
Dr. Teunissen has functioned in advisory boards of Fujirebio and Roche, received nonfinancial support in the form of research consumables from ADxNeurosciences and Euroimmun, performed contract research or received grants from Probiodrug , Janssen Prevention Center , Boehringer , Brains Online , Axon Neurosciences , EIP Pharma , and Roche . Dr. Martinez-Lage reports personal fees from Lilly, Axon, General Electric, and Nutricia for advisory boards and lecturing fees from Lilly, Nutricia, and Piramal. Dr. Blennow has served as a consultant or at advisory boards for Fujirebio Europe, IBL International, and Roche Diagnostics and is a cofounder of Brain Biomarker Solutions in Gothenburg AB, a GU Venture–based platform company at the University of Gothenburg. The other authors declare no conflict of interest.
Funding Information:
The present study was conducted as part of the EMIF-AD project which has received support from the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement n° 115372, resources of which are composed of financial contribution from the European Union's Seventh Framework Program ( FP7/2007-2013 ) and EFPIA companies' in kind contribution. The DESCRIPA study was funded by the European Commission within the fifth framework program ( QLRT-2001-2455 ). The EDAR study was funded by the European Commission within the fifth framework program (contract # 37,670). The San Sebastian GAP study is partially funded by the Department of Health of the Basque Government (allocation 17.0.1.08.12.0000.2.454.01.41142.001.H). The Lausanne center study was supported by a grant from the Swiss National Research Foundation to J.P. ( SNF 320030_141179 ). K.S. is supported by het University of Antwerp Research Fund , Belgium. F.B. is supported by the NIHR UCLH biomedical research center . K.B. holds the Torsten Söderberg Professorship in medicine at the Swedish Royal Academy of Science. H.Z. is a Wallenberg Academy Fellow. The GAP study is supported by grants from the Department of Economic Promotion, Rural Areas and Territorial Balance of the Provincial Government of Gipuzkoa (124/16); the Department of Health of the Basque Government ( 2016111096 ); and by the Carlos III Institute of Health (PI15/00,919, PN de I + D + I 2013-2016); Obra Social Kutxa-Fundazioa ; and anonymous private donors. C.T. received grants from the European Commission , the Dutch Research Council (ZonMW) , Association of Frontotemporal Dementia/ Alzheimer's Drug Discovery Foundation , Alzheimer Netherlands .
Publisher Copyright:
© 2019 the Alzheimer's Association
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2019/5
Y1 - 2019/5
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.
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 - Journal articles
C2 - 30853464
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 -
