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EMBO Mol Med. 2016 May 2;8(5):466-76. doi: 10.15252/emmm.201506123. Print 2016 May.

sTREM2 cerebrospinal fluid levels are a potential biomarker for microglia activity in early-stage Alzheimer's disease and associate with neuronal injury markers.

Author information

1
BioMedical Center (BMC), Biochemistry, Ludwig-Maximilians-University Munich, Munich, Germany German Center for Neurodegenerative Diseases (DZNE) Munich, Munich, Germany.
2
BioMedical Center (BMC), Biochemistry, Ludwig-Maximilians-University Munich, Munich, Germany Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
3
Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University Munich, Munich, Germany.
4
Department of Nuclear Medicine, Klinikum der Universität München, Ludwig-Maximilians-University Munich, Munich, Germany.
5
Munich Cluster for Systems Neurology (SyNergy), Munich, Germany Department of Nuclear Medicine, Klinikum der Universität München, Ludwig-Maximilians-University Munich, Munich, Germany.
6
Department of Neurology, Institut d'Investigacions Biomèdiques Hospital de la Santa Creu i Sant Pau Universitat Autònoma de Barcelona, Barcelona, Spain Center for Networked Biomedical Research for Neurodegenerative Diseases, CIBERNED, Madrid, Spain.
7
Clinical and Neuroimaging Departments, Barcelona Beta Brain Research Center Pasqual Maragall Foundation, Barcelona, Spain Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Barcelona, Spain.
8
Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, ICN Hospital Clinic i Universitari, Barcelona, Spain Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
9
Clinical and Neuroimaging Departments, Barcelona Beta Brain Research Center Pasqual Maragall Foundation, Barcelona, Spain Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Barcelona, Spain Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, ICN Hospital Clinic i Universitari, Barcelona, Spain Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
10
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
11
Neurology Department, Universitätsklinikum Bonn, Bonn, Germany.
12
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany Neurology Department, Universitätsklinikum Bonn, Bonn, Germany.
13
Reference Center for Biological Markers of Dementia (BIODEM), Laboratory of Neurochemistry and Behavior, Institute Born-Bunge University of Antwerp, Antwerp, Belgium Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium.
14
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium Laboratory of Neurogenetics, Institute Born-Bunge University of Antwerp, Antwerp, Belgium.
15
Clinical Neurochemistry Lab, Institute of Neuroscience and Physiology The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden Reta Lila Weston Laboratories and Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
16
Department of Anaesthesiology and Intensive Care, Institute of Clinical Sciences Sahlgrenska Academy Gothenburg University, Gothenburg, Sweden.
17
Clinical Neurochemistry Lab, Institute of Neuroscience and Physiology The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
18
Institute of Medical Informatics, Biometry, and Epidemiology, Munich, Germany.
19
Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University Munich, Munich, Germany michael.ewers@med.uni-muenchen.de christian.haass@mail03.med.uni-muenchen.de.
20
BioMedical Center (BMC), Biochemistry, Ludwig-Maximilians-University Munich, Munich, Germany German Center for Neurodegenerative Diseases (DZNE) Munich, Munich, Germany Munich Cluster for Systems Neurology (SyNergy), Munich, Germany michael.ewers@med.uni-muenchen.de christian.haass@mail03.med.uni-muenchen.de.

Abstract

TREM2 is an innate immune receptor expressed on the surface of microglia. Loss-of-function mutations of TREM2 are associated with increased risk of Alzheimer's disease (AD). TREM2 is a type-1 protein with an ectodomain that is proteolytically cleaved and released into the extracellular space as a soluble variant (sTREM2), which can be measured in the cerebrospinal fluid (CSF). In this cross-sectional multicenter study, we investigated whether CSF levels of sTREM2 are changed during the clinical course of AD, and in cognitively normal individuals with suspected non-AD pathology (SNAP). CSF sTREM2 levels were higher in mild cognitive impairment due to AD than in all other AD groups and controls. SNAP individuals also had significantly increased CSF sTREM2 compared to controls. Moreover, increased CSF sTREM2 levels were associated with higher CSF total tau and phospho-tau181P, which are markers of neuronal degeneration and tau pathology. Our data demonstrate that CSF sTREM2 levels are increased in the early symptomatic phase of AD, probably reflecting a corresponding change of the microglia activation status in response to neuronal degeneration.

KEYWORDS:

Alzheimer's disease; TREM2; biomarkers; microglia; neurodegeneration

PMID:
26941262
PMCID:
PMC5120370
DOI:
10.15252/emmm.201506123
[Indexed for MEDLINE]
Free PMC Article

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