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

被引：91

作者：

Bos, Isabelle ^{[1
]}

Vos, Stephanie ^{[1
]}

Verhey, Frans ^{[1
]}

Scheltens, Philip ^{[2
]}

Teunissen, Charlotte ^{[3
,4
]}

Engelborghs, Sebastiaan ^{[5
,6
,7
,8
]}

Sleegers, Kristel ^{[8
,9
]}

Frisoni, Giovanni ^{[10
,11
]}

Blin, Olivier ^{[12
]}

Richardson, Jill C. ^{[13
]}

Bordet, Regis ^{[14
]}

Tsolaki, Magda ^{[15
]}

Popp, Julius ^{[16
,17
]}

Peyratout, Gwendoline ^{[17
]}

Martinez-Lage, Pablo ^{[18
]}

Tainta, Mikel ^{[18
]}

Lleo, Alberto ^{[19
]}

Johannsen, Peter ^{[20
]}

Freund-Levi, Yvonne ^{[21
,22
,23
]}

Froelich, Lutz ^{[24
]}

Vandenberghe, Rik ^{[25
]}

Westwood, Sarah ^{[26
]}

Dobricic, Valerija ^{[27
]}

Barkhof, Frederik ^{[28
,29
,30
]}

Legido-Quigley, Cristina ^{[31
,32
]}

Bertram, Lars ^{[27
,33
,34
]}

Lovestone, Simon ^{[26
]}

Streffer, Johannes ^{[7
,35
,40
]}

Andreasson, Ulf ^{[36
,37
]}

Blennow, Kaj ^{[36
,37
]}

Zetterberg, Henrik ^{[36
,37
,38
,39
]}

Visser, Pieter Jelle ^{[1
,2
]}

机构：

[1] Maastricht Univ, Alzheimer Ctr Limburg, Maastricht, Netherlands

[2] Vrije Univ Amsterdam Med Ctr, Alzheimer Ctr, Amsterdam, Netherlands

[3] Vrije Univ Amsterdam Med Ctr, Dept Clin Chem, Neurochem Lab, Amsterdam Neurosci, Amsterdam, Netherlands

[4] Vrije Univ Amsterdam Med Ctr, Dept Clin Chem, Biobank, Amsterdam Neurosci, Amsterdam, Netherlands

[5] Hosp Network Antwerp ZNA Middelhe & Hoge Beuken, Dept Neurol, Antwerp, Belgium

[6] Hosp Network Antwerp ZNA Middelhe & Hoge Beuken, Memory Clin, Antwerp, Belgium

[7] Univ Antwerp, Reference Ctr Biol Markers Dementia BIODEM, Inst Born Bunge, Antwerp, Belgium

[8] Univ Antwerp, Inst Born Bunge, Antwerp, Belgium

[9] VIB, Ctr Mol Neurol, Neurodegenerat Brain Dis Grp, Antwerp, Belgium

[10] Univ Geneva, Geneva, Switzerland

[11] IRCCS Ist Ctr San Giovanni di Dio Fatebenefratell, Brescia, Italy

[12] Aix Marseille Univ, Mediterranean Inst Cognit Neurosci, Marseille, France

[13] GlaxoSmithKline R&D, Neurosci Therapeut Area, Stevenage, Herts, England

[14] Univ Lille, CHU Lille, INSERM, Lille, France

[15] AHEPA Univ Hosp, Dept Neurol 1, Thessaloniki, Greece

[16] Geneva Univ Hosp, Dept Mental Hlth & Psychiat, Geriatr Psychiat, Geneva, Switzerland

[17] Univ Hosp Lausanne, Dept Psychiat, Lausanne, Switzerland

[18] CITA Alzheimer Fdn, Ctr Res & Adv Therapies, Dept Neurol, San Sebastian, Spain

[19] Hosp Santa Creu & Sant Pau, Barcelona, Spain

[20] Copenhagen Univ Hosp, Rigshosp, Danish Dementia Res Ctr, Copenhagen, Denmark

[21] Karolinska Inst, Dept Neurobiol Caring Sci & Soc NVS, Div Clin Geriatr, Stockholm, Sweden

[22] Karolinska Univ Hosp Huddinge, Dept Geriatr Med, Stockholm, Sweden

[23] Norrtalje Hosp Tiohundra, Dept Psychiat, Norrtaije, Sweden

[24] Heidelberg Univ, Zent Inst Seel Gesundheit, Dept Geriatr Psychiat, Mannheim, Germany

[25] Univ Hosp Leuven, Leuven, Belgium

[26] Univ Oxford, Oxford, England

[27] Univ Lubeck, Lubeck Interdisciplinary Platform Genome Analyt, Lubeck, Germany

[28] Vrije Univ Amsterdam Med Ctr, Dept Radiol & Nucl Med, Amsterdam, Netherlands

[29] UCL, Inst Neurol, London, England

[30] UCL, Inst Healthcare Engn, London, England

[31] Steno Diabet Ctr, Copenhagen, Denmark

[32] Kings Coll London, London, England

[33] Imperial Coll London, Sch Publ Hlth, London, England

[34] Univ Oslo, Dept Psychol, Oslo, Norway

[35] UCB Biopharma SPRL, Early Clinial Neurol, Braine Lalleud, Belgium

[36] Sahlgrens Univ Hosp, Inst Neurosci & Physiol, Clin Neurochem Lab, Molndal, Sweden

[37] Univ Gothenburg, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden

[38] UCL Inst Neurol, Dept Mol Neurosci, London, England

[39] UK Dementia Res Inst, London, England

[40] Janssen R&D LLC, Beerse, Belgium

来源：

ALZHEIMERS & DEMENTIA | 2019年 / 15卷 / 05期

基金：

新加坡国家研究基金会; 荷兰研究理事会;

关键词：

Alzheimer's disease; Amyloid-beta; Neurofilament light; Neurogranin; YKL-40; Cognition; Cerebrospinal fluid; APOE; MILD COGNITIVE IMPAIRMENT; NEUROFILAMENT LIGHT; NEUROGRANIN; PROTEIN; PATHOLOGY; YKL-40; TAU; DEGENERATION; ASSOCIATION; GUIDELINES;

D O I：

10.1016/j.jalz.2019.01.004

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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.

引用

页码：644 / 654

页数：11

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