Ludwig-Maximilians-Universität, Chair of Metabolic Biochemistry

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

EMBO Mol Med. 2016 May 2;8(5):466-76

Authors/Editors: 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 Nellgard
Kaj Blennow
Alexander Crispin
Michael Ewers
Christian Haass
Publication Date: 2016
Type of Publication: Journal Article

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 crosssectional 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.


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