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Alzheimers Dement. 2019 Mar 7. pii: S1552-5260(19)30018-4. doi: 10.1016/j.jalz.2019.01.004. [Epub ahead of print]

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

Author information

1
Alzheimer Centrum Limburg, Maastricht University, Maastricht, the Netherlands. Electronic address: isabelle.bos@maastrichtuniversity.nl.
2
Alzheimer Centrum Limburg, Maastricht University, Maastricht, the Netherlands.
3
Alzheimer Center, VU University Medical Center, Amsterdam, the Netherlands.
4
Neurochemistry Lab and Biobank, Department of Clinical Chemistry, VU University Medical Center, Amsterdam Neuroscience, Amsterdam, the Netherlands.
5
Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium; Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
6
Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; Neurodegenerative Brain Diseases Group, Center for Molecular Neurology, VIB, Antwerp, Belgium.
7
University of Geneva, Geneva, Switzerland; IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
8
Mediterranean Institute of Cognitive Neuroscience, Aix Marseille University, Marseille, France.
9
Neurosciences Therapeutic Area, GlaxoSmithKline R&D, Stevenage, UK.
10
University of Lille, Inserm, CHU Lille, Lille, France.
11
1st Department of Neurology, AHEPA University Hospital, Makedonia, Thessaloniki, Greece.
12
Geriatric Psychiatry, Department of Mental Health and Psychiatry, Geneva University Hospitals, Geneva, Switzerland; Department of Psychiatry, University Hospital of Lausanne, Lausanne, Switzerland.
13
Department of Psychiatry, University Hospital of Lausanne, Lausanne, Switzerland.
14
Department of Neurology, Center for Research and Advanced Therapies, CITA-Alzheimer Foundation, San Sebastian, Spain.
15
Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
16
Danish Dementia Research Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
17
Department of Neurobiology, Caring Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden; Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden; Department of Psychiatry Norrtälje Hospital Tiohundra, Norrtäije, Sweden.
18
Department of Geriatric Psychiatry, Zentralinstitut für Seelische Gesundheit, University of Heidelberg, Mannheim, Germany.
19
University Hospital Leuven, Leuven, Belgium.
20
University of Oxford, Oxford, United Kingdom.
21
Lübeck Interdisciplinary Platform for Genome Analytics, University of Lübeck, Lübeck, Germany.
22
Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands; Institutes of Neurology and Healthcare Engineering, University College London, London, UK.
23
Steno Diabetes Center, Copenhagen, Denmark; King's College London, London, UK.
24
Lübeck Interdisciplinary Platform for Genome Analytics, University of Lübeck, Lübeck, Germany; School of Public Health, Imperial College London, London, UK; Department of Psychology, University of Oslo, Oslo, Norway.
25
Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; Early Clinial Neurology, UCB Biopharma SPRL, Braine-l'Alleud, Belgium.
26
Clinical Neurochemistry Lab, Institute of Neuroscience and Physiology, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Psychiatry and Neurochemistry, University of Gothenburg, Institute of Neuroscience and Physiology, Mölndal, Sweden.
27
Clinical Neurochemistry Lab, Institute of Neuroscience and Physiology, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Psychiatry and Neurochemistry, University of Gothenburg, Institute of Neuroscience and Physiology, Mölndal, Sweden; Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK; UK Dementia Research Institute, London, UK.
28
Alzheimer Centrum Limburg, Maastricht University, Maastricht, the Netherlands; Alzheimer Center, VU University Medical Center, Amsterdam, the Netherlands.

Abstract

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.

KEYWORDS:

APOE; Alzheimer's disease; Amyloid-β; Cerebrospinal fluid; Cognition; Neurofilament light; Neurogranin; YKL-40

PMID:
30853464
DOI:
10.1016/j.jalz.2019.01.004

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