Open AccesssTREM 2 cerebrospinal fluid levels are a potential biomarker for microglia activity in early‐stage Alzheimer's disease and associate with neuronal injury markers
Author(s) -
SuárezCalvet Marc,
Kleinberger Gernot,
Araque Caballero Miguel Ángel,
Brendel Matthias,
Rominger Axel,
Alcolea Daniel,
Fortea Juan,
Lleó Alberto,
Blesa Rafael,
Gispert Juan Domingo,
SánchezValle Raquel,
Antonell Anna,
Rami Lorena,
Molinuevo José L,
Brosseron Frederic,
Traschütz Andreas,
Heneka Michael T,
Struyfs Hanne,
Engelborghs Sebastiaan,
Sleegers Kristel,
Van Broeckhoven Christine,
Zetterberg Henrik,
Nellgård Bengt,
Blennow Kaj,
Crispin Alexander,
Ewers Michael,
Haass Christian
Publication year - 2016
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201506123
Subject(s) - microglia , cerebrospinal fluid , biomarker , alzheimer's disease , medicine , disease , traumatic brain injury , stage (stratigraphy) , pathology , immunology , inflammation , biology , biochemistry , paleontology , psychiatry
TREM 2 is an innate immune receptor expressed on the surface of microglia. Loss‐of‐function mutations of TREM 2 are associated with increased risk of Alzheimer's disease ( AD ). TREM 2 is a type‐1 protein with an ectodomain that is proteolytically cleaved and released into the extracellular space as a soluble variant ( sTREM 2), which can be measured in the cerebrospinal fluid ( CSF ). In this cross‐sectional multicenter study, we investigated whether CSF levels of sTREM 2 are changed during the clinical course of AD , and in cognitively normal individuals with suspected non‐ AD pathology ( SNAP ). CSF sTREM 2 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 sTREM 2 compared to controls. Moreover, increased CSF sTREM 2 levels were associated with higher CSF total tau and phospho‐tau 181P , which are markers of neuronal degeneration and tau pathology. Our data demonstrate that CSF sTREM 2 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.