EMBO Molecular Medicine (Mar 2016)
sTREM2 cerebrospinal fluid levels are a potential biomarker for microglia activity in early‐stage Alzheimer's disease and associate with neuronal injury markers
- Marc Suárez‐Calvet,
- Gernot Kleinberger,
- Miguel Ángel Araque Caballero,
- Matthias Brendel,
- Axel Rominger,
- Daniel Alcolea,
- Juan Fortea,
- Alberto Lleó,
- Rafael Blesa,
- Juan Domingo Gispert,
- Raquel Sánchez‐Valle,
- Anna Antonell,
- Lorena Rami,
- José L Molinuevo,
- Frederic Brosseron,
- Andreas Traschütz,
- Michael T Heneka,
- Hanne Struyfs,
- Sebastiaan Engelborghs,
- Kristel Sleegers,
- Christine Van Broeckhoven,
- Henrik Zetterberg,
- Bengt Nellgård,
- Kaj Blennow,
- Alexander Crispin,
- Michael Ewers,
- Christian Haass
Affiliations
- Marc Suárez‐Calvet
- BioMedical Center (BMC), Biochemistry, Ludwig‐Maximilians‐University Munich
- Gernot Kleinberger
- BioMedical Center (BMC), Biochemistry, Ludwig‐Maximilians‐University Munich
- Miguel Ángel Araque Caballero
- Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig‐Maximilians‐University Munich
- Matthias Brendel
- Department of Nuclear Medicine, Klinikum der Universität München, Ludwig‐Maximilians‐University Munich
- Axel Rominger
- Munich Cluster for Systems Neurology (SyNergy)
- Daniel Alcolea
- Department of Neurology, Institut d'Investigacions Biomèdiques, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona
- Juan Fortea
- Department of Neurology, Institut d'Investigacions Biomèdiques, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona
- Alberto Lleó
- Department of Neurology, Institut d'Investigacions Biomèdiques, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona
- Rafael Blesa
- Department of Neurology, Institut d'Investigacions Biomèdiques, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona
- Juan Domingo Gispert
- Clinical and Neuroimaging Departments, Barcelona Beta Brain Research Center, Pasqual Maragall Foundation
- Raquel Sánchez‐Valle
- Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, ICN Hospital Clinic i Universitari
- Anna Antonell
- Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, ICN Hospital Clinic i Universitari
- Lorena Rami
- Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, ICN Hospital Clinic i Universitari
- José L Molinuevo
- Clinical and Neuroimaging Departments, Barcelona Beta Brain Research Center, Pasqual Maragall Foundation
- Frederic Brosseron
- German Center for Neurodegenerative Diseases (DZNE)
- Andreas Traschütz
- Neurology Department, Universitätsklinikum Bonn
- Michael T Heneka
- German Center for Neurodegenerative Diseases (DZNE)
- Hanne Struyfs
- Reference Center for Biological Markers of Dementia (BIODEM), Laboratory of Neurochemistry and Behavior, Institute Born‐Bunge, University of Antwerp
- Sebastiaan Engelborghs
- Reference Center for Biological Markers of Dementia (BIODEM), Laboratory of Neurochemistry and Behavior, Institute Born‐Bunge, University of Antwerp
- Kristel Sleegers
- Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB
- Christine Van Broeckhoven
- Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB
- Henrik Zetterberg
- Clinical Neurochemistry Lab, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg
- Bengt Nellgård
- Department of Anaesthesiology and Intensive Care, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg University
- Kaj Blennow
- Clinical Neurochemistry Lab, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg
- Alexander Crispin
- Institute of Medical Informatics, Biometry, and Epidemiology
- Michael Ewers
- Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig‐Maximilians‐University Munich
- Christian Haass
- BioMedical Center (BMC), Biochemistry, Ludwig‐Maximilians‐University Munich
- DOI
- https://doi.org/10.15252/emmm.201506123
- Journal volume & issue
-
Vol. 8,
no. 5
pp. 466 – 476
Abstract
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
