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Alzheimers Dement. 2019 Jun;15(6):776-787. doi: 10.1016/j.jalz.2019.03.007. Epub 2019 Apr 30.

Inflammatory biomarkers in Alzheimer's disease plasma.

Author information

1
Systems Immunity Research Institute and UK Dementia Research Institute Cardiff, School of Medicine, Cardiff University, Cardiff, UK.
2
Department of Psychiatry, University of Oxford, Oxford, UK.
3
Department of Radiology and Nuclear Medicine, VU University Medical, Amsterdam, the Netherlands; UCL Institutes of Neurology and Healthcare Engineering, University College London, London, UK.
4
Max Planck Institute for Molecular Genetics, Berlin, Germany.
5
Aix-Marseille University, APHM, Institute Neurosci System, Pharmacology, Marseille, France.
6
Alzheimer Centrum Limburg, Maastricht University, Maastricht, the Netherlands.
7
Lübeck Interdisciplinary Platform for Genome Analytics, University of Lübeck, Lübeck, Germany.
8
Department of Neurology, Hospital Network Antwerp (ZNA), Antwerp, Belgium; Reference Center for Biological Markers of Dementia, Institute Born-Bunge, Antwerp, Belgium.
9
University of Geneva, Geneva, Switzerland; IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
10
Department of Geriatric Psychiatry, Zentralinstitut für Seelische Gesundheit, University of Heidelberg, Mannheim, Germany.
11
Department of Neurosciences, Laboratory for Cognitive Neurology, KU Leuven, Leuven, Belgium.
12
Division of Clinical Geriatrics, Department of Neurobiology, Caring Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
13
University of Gothenburg, Institute of Neuroscience and Physiology, Gothenburg, Sweden.
14
Department of Old Age Psychiatry & Psychotic Disorders, Medical University of Lodz, Lodz, Poland.
15
UCL Institutes of Neurology and Healthcare Engineering, University College London, London, UK; School of Public Health, Imperial College London, London, UK.
16
Department of Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
17
CITA-Alzheimer Foundation, San Sebastian, Spain.
18
Department of Medicine, Institute of Gerontology and Geriatrics, University of Perugia, Perugia, Italy.
19
Barcelona Beta Brain Research Center, Unversitat Pompeu Fabra, Barcelona, Spain.
20
Department of Psychiatry, Old Age Psychiatry, Lausanne University Hospital, Lausanne, Switzerland.
21
Hopitaux Universitaires Geneve and Universite de Geneve, Geneva, Switzerland.
22
Neurosciences Therapeutic Area, GlaxoSmithKline R&D, Stevenage, UK.
23
Memory Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
24
Alzheimer Center, Amsterdam University Medical Centers, Vrije Universiteit, Amsterdam, the Netherlands.
25
Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
26
Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland.
27
Center for Research and Advanced Therapies. CITA-Alzheimer Foundation, San Sebastian, Spain.
28
University Hospital Leuven, Leuven, Belgium.
29
1st Department of Neurology, AHEPA University Hospital, Makedonia, Thessaloniki, Greece.
30
Department of Clinical Chemistry, Neurochemistry lab, Amsterdam University Medical Centers, Amsterdam, the Netherlands.
31
Department of Psychiatry & Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands.
32
NVS-Department, Section of Clinical Geriatrics, Karolinska Institutet, Huddinge, Sweden.
33
Section for Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg Sahlgrenska Academy, Gothenburg, Sweden.
34
Clinical Neurochemistry Lab, Institute of Neuroscience and Physiology, Sahlgrenska University Hospital, Mölndal, Sweden; Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, University of Gothenburg, Mölndal, Sweden; Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK; UK Dementia Research Institute, London, UK.
35
Systems Immunity Research Institute and UK Dementia Research Institute Cardiff, School of Medicine, Cardiff University, Cardiff, UK. Electronic address: morganbp@cardiff.ac.uk.

Abstract

INTRODUCTION:

Plasma biomarkers for Alzheimer's disease (AD) diagnosis/stratification are a "Holy Grail" of AD research and intensively sought; however, there are no well-established plasma markers.

METHODS:

A hypothesis-led plasma biomarker search was conducted in the context of international multicenter studies. The discovery phase measured 53 inflammatory proteins in elderly control (CTL; 259), mild cognitive impairment (MCI; 199), and AD (262) subjects from AddNeuroMed.

RESULTS:

Ten analytes showed significant intergroup differences. Logistic regression identified five (FB, FH, sCR1, MCP-1, eotaxin-1) that, age/APOε4 adjusted, optimally differentiated AD and CTL (AUC: 0.79), and three (sCR1, MCP-1, eotaxin-1) that optimally differentiated AD and MCI (AUC: 0.74). These models replicated in an independent cohort (EMIF; AUC 0.81 and 0.67). Two analytes (FB, FH) plus age predicted MCI progression to AD (AUC: 0.71).

DISCUSSION:

Plasma markers of inflammation and complement dysregulation support diagnosis and outcome prediction in AD and MCI. Further replication is needed before clinical translation.

KEYWORDS:

Alzheimer's disease; Biomarker; Complement; Inflammation; Plasma

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