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Alzheimers Dement. 2019 Sep 5. pii: S1552-5260(19)35118-0. doi: 10.1016/j.jalz.2019.06.4951. [Epub ahead of print]

Discovery and validation of plasma proteomic biomarkers relating to brain amyloid burden by SOMAscan assay.

Author information

1
Department of Psychiatry, University of Oxford, Oxford, UK. Electronic address: liu.shi@psych.ox.ac.uk.
2
Department of Psychiatry, University of Oxford, Oxford, UK.
3
Lübeck Interdisciplinary Platform for Genome Analytics, Institutes of Neurogenetics and Cardiogenetics, University of Lübeck, Lübeck, Germany.
4
Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
5
Maurice Wohl Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, UK.
6
Maurice Wohl Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, UK; Department of Psychiatry and Neurochemistry, University of Gothenburg, Mölndal, Sweden; Wallenberg Centre for Molecular & Translational Medicine, University of Gothenburg, Gothenburg, Sweden; NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, UK.
7
Dementia Research Institute Cardiff, Cardiff University, Cardiff, UK.
8
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Centrum Limburg, Maastricht University, Maastricht, the Netherlands.
9
Alzheimer Center, VU University Medical Center, Amsterdam, the Netherlands.
10
University Hospital Leuven, Leuven, Belgium.
11
University Hospital Leuven, Leuven, Belgium; Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Belgium.
12
Center for Neurosciences, Vrije Universiteit Brussel (VUB), Brussels, Belgium; Reference Center for Biological Markers of Dementia (BIODEM), University of Antwerp, Antwerp, Belgium; Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; Department of Neurology, VUB University Hospital Brussels (UZ Brussel), Brussels, Belgium.
13
Center for Neurosciences, Vrije Universiteit Brussel (VUB), Brussels, Belgium; Reference Center for Biological Markers of Dementia (BIODEM), University of Antwerp, Antwerp, Belgium; Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
14
Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; Neurodegenerative Brain Diseases Group, Center for Molecular Neurology, VIB, Edegem, Belgium.
15
University of Geneva, Geneva, Switzerland; IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
16
AIX Marseille University, INS, Ap-hm, Marseille, France.
17
Neurosciences Therapeutic Area, GlaxoSmithKline R&D, Stevenage, UK.
18
University of Lille, Inserm, CHU Lille, Lille, France.
19
Alzheimer's disease & other cognitive disorders unit, Hopsital Clínic-IDIBAPS, Barcelona, Spain; Barcelona Beta Brain Research Center, Universitat Pompeu Fabra, Barcelona, Spain.
20
Barcelona Beta Brain Research Center, Universitat Pompeu Fabra, Barcelona, Spain.
21
Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
22
Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
23
1st Department of Neurology, AHEPA University Hospital, Makedonia, Thessaloniki, Greece.
24
Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
25
Department of Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
26
University Hospital of Lausanne, Lausanne, Switzerland; Geriatric Psychiatry, Department of Mental Health and Psychiatry, Geneva University Hospitals, Geneva, Switzerland.
27
University Hospital of Lausanne, Lausanne, Switzerland.
28
CITA-Alzheimer Foundation, San Sebastian, Spain.
29
Danish Dementia Research Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
30
Neurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit, Amsterdam, The Netherlands.
31
Department of Neurobiology, Caring Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institutet, and Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden; Department of Psychiatry in Region Örebro County and School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Department of Old Age Psychiatry, Psychology and Neuroscience, Kings College London, London, UK.
32
Department of Geriatric Psychiatry, Zentralinstitut für Seelische Gesundheit, University of Heidelberg, Mannheim, Germany.
33
Kings College London, London, UK; The Systems Medicine Group, Steno Diabetes Center, Gentofte, Denmark.
34
Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherland; UCL Institutes of Neurology and Healthcare Engineering, London, UK.
35
Department of Psychiatry and Neurochemistry, University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
36
Department of Psychiatry and Neurochemistry, University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; UK Dementia Research Institute at UCL, London, UK; Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
37
Janssen R&D, Titusville, NJ, USA.
38
Reference Center for Biological Markers of Dementia (BIODEM), University of Antwerp, Antwerp, Belgium; Janssen R&D, LLC, Beerse, Belgium.
39
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Centrum Limburg, Maastricht University, Maastricht, the Netherlands; Alzheimer Center, VU University Medical Center, Amsterdam, the Netherlands; Department of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics, Karolinska Institutet, Stockholm, Sweden.
40
Lübeck Interdisciplinary Platform for Genome Analytics, Institutes of Neurogenetics and Cardiogenetics, University of Lübeck, Lübeck, Germany; Department of Psychology, University of Oslo, Oslo, Norway.
41
Department of Psychiatry, University of Oxford, Oxford, UK; Janssen-Cilag UK, formerly Department of Psychiatry, University of Oxford, Oxford, UK.

Abstract

INTRODUCTION:

Plasma proteins have been widely studied as candidate biomarkers to predict brain amyloid deposition to increase recruitment efficiency in secondary prevention clinical trials for Alzheimer's disease. Most such biomarker studies are targeted to specific proteins or are biased toward high abundant proteins.

METHODS:

4001 plasma proteins were measured in two groups of participants (discovery group = 516, replication group = 365) selected from the European Medical Information Framework for Alzheimer's disease Multimodal Biomarker Discovery study, all of whom had measures of amyloid.

RESULTS:

A panel of proteins (n = 44), along with age and apolipoprotein E (APOE) ε4, predicted brain amyloid deposition with good performance in both the discovery group (area under the curve = 0.78) and the replication group (area under the curve = 0.68). Furthermore, a causal relationship between amyloid and tau was confirmed by Mendelian randomization.

DISCUSSION:

The results suggest that high-dimensional plasma protein testing could be a useful and reproducible approach for measuring brain amyloid deposition.

KEYWORDS:

Amyloid β; Causal relationship; Plasma proteomics; Replication; SOMAscan assay; Tau

PMID:
31495601
DOI:
10.1016/j.jalz.2019.06.4951
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