Cerebrospinal fluid biomarkers of neurodegeneration, synaptic integrity, and astroglial activation across the clinical Alzheimer's disease spectrum
Por:
Bos, I, Vos, S, Verhey, F, Scheltens, P, Teunissen, C, Engelborghs, S, Sleegers, K, Frisoni, G, Blin, O, Richardson, JC, Bordet, R, Tsolaki, M, Popp, J, Peyratout, G, Martinez-Lage, P, Tainta, M, Lleo, A, Johannsen, P, Freund-Levi, Y, Frolich, L, Vandenberghe, R, Westwood, S, Dobricic, V, Barkhof, F, Legido-Quigley, C, Bertram, L, Lovestone, S, Streffer, J, Andreasson, U, Blennow, K, Zetterberg, H, Visser, PJ
Publicada:
1 may 2019
Resumen:
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.
Filiaciones:
Bos, I:
Maastricht Univ, Alzheimer Ctr Limburg, Maastricht, Netherlands
Vos, S:
Maastricht Univ, Alzheimer Ctr Limburg, Maastricht, Netherlands
Verhey, F:
Maastricht Univ, Alzheimer Ctr Limburg, Maastricht, Netherlands
Scheltens, P:
Vrije Univ Amsterdam Med Ctr, Alzheimer Ctr, Amsterdam, Netherlands
Teunissen, C:
Vrije Univ Amsterdam Med Ctr, Dept Clin Chem, Neurochem Lab, Amsterdam Neurosci, Amsterdam, Netherlands
Vrije Univ Amsterdam Med Ctr, Dept Clin Chem, Biobank, Amsterdam Neurosci, Amsterdam, Netherlands
Engelborghs, S:
Hosp Network Antwerp ZNA Middelhe & Hoge Beuken, Dept Neurol, Antwerp, Belgium
Hosp Network Antwerp ZNA Middelhe & Hoge Beuken, Memory Clin, Antwerp, Belgium
Univ Antwerp, Reference Ctr Biol Markers Dementia BIODEM, Inst Born Bunge, Antwerp, Belgium
Univ Antwerp, Inst Born Bunge, Antwerp, Belgium
Sleegers, K:
Univ Antwerp, Inst Born Bunge, Antwerp, Belgium
VIB, Ctr Mol Neurol, Neurodegenerat Brain Dis Grp, Antwerp, Belgium
Frisoni, G:
Univ Geneva, Geneva, Switzerland
IRCCS Ist Ctr San Giovanni di Dio Fatebenefratell, Brescia, Italy
Blin, O:
Aix Marseille Univ, Mediterranean Inst Cognit Neurosci, Marseille, France
Richardson, JC:
GlaxoSmithKline R&D, Neurosci Therapeut Area, Stevenage, Herts, England
Bordet, R:
Univ Lille, CHU Lille, INSERM, Lille, France
Tsolaki, M:
AHEPA Univ Hosp, Dept Neurol 1, Thessaloniki, Greece
Popp, J:
Geneva Univ Hosp, Dept Mental Hlth & Psychiat, Geriatr Psychiat, Geneva, Switzerland
Univ Hosp Lausanne, Dept Psychiat, Lausanne, Switzerland
Peyratout, G:
Univ Hosp Lausanne, Dept Psychiat, Lausanne, Switzerland
Martinez-Lage, P:
CITA Alzheimer Fdn, Ctr Res & Adv Therapies, Dept Neurol, San Sebastian, Spain
Tainta, M:
CITA Alzheimer Fdn, Ctr Res & Adv Therapies, Dept Neurol, San Sebastian, Spain
Lleo, A:
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Johannsen, P:
Copenhagen Univ Hosp, Rigshosp, Danish Dementia Res Ctr, Copenhagen, Denmark
Freund-Levi, Y:
Karolinska Inst, Dept Neurobiol Caring Sci & Soc NVS, Div Clin Geriatr, Stockholm, Sweden
Karolinska Univ Hosp Huddinge, Dept Geriatr Med, Stockholm, Sweden
Norrtalje Hosp Tiohundra, Dept Psychiat, Norrtaije, Sweden
Frolich, L:
Heidelberg Univ, Zent Inst Seel Gesundheit, Dept Geriatr Psychiat, Mannheim, Germany
Vandenberghe, R:
Univ Hosp Leuven, Leuven, Belgium
Westwood, S:
Univ Oxford, Oxford, England
Dobricic, V:
Univ Lubeck, Lubeck Interdisciplinary Platform Genome Analyt, Lubeck, Germany
Barkhof, F:
Vrije Univ Amsterdam Med Ctr, Dept Radiol & Nucl Med, Amsterdam, Netherlands
UCL, Inst Neurol, London, England
UCL, Inst Healthcare Engn, London, England
Legido-Quigley, C:
Steno Diabet Ctr, Copenhagen, Denmark
Kings Coll London, London, England
Bertram, L:
Univ Lubeck, Lubeck Interdisciplinary Platform Genome Analyt, Lubeck, Germany
Imperial Coll London, Sch Publ Hlth, London, England
Univ Oslo, Dept Psychol, Oslo, Norway
Lovestone, S:
Univ Oxford, Oxford, England
Streffer, J:
Univ Antwerp, Reference Ctr Biol Markers Dementia BIODEM, Inst Born Bunge, Antwerp, Belgium
UCB Biopharma SPRL, Early Clinial Neurol, Braine Lalleud, Belgium
Janssen R&D LLC, Beerse, Belgium
Andreasson, U:
Sahlgrens Univ Hosp, Inst Neurosci & Physiol, Clin Neurochem Lab, Molndal, Sweden
Univ Gothenburg, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden
Blennow, K:
Sahlgrens Univ Hosp, Inst Neurosci & Physiol, Clin Neurochem Lab, Molndal, Sweden
Univ Gothenburg, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden
Zetterberg, H:
Sahlgrens Univ Hosp, Inst Neurosci & Physiol, Clin Neurochem Lab, Molndal, Sweden
Univ Gothenburg, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden
UCL Inst Neurol, Dept Mol Neurosci, London, England
UK Dementia Res Inst, London, England
Visser, PJ:
Maastricht Univ, Alzheimer Ctr Limburg, Maastricht, Netherlands
Vrije Univ Amsterdam Med Ctr, Alzheimer Ctr, Amsterdam, Netherlands
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