Higher CSF sTREM2 and microglia activation are associated with slower rates of beta-amyloid accumulation

Michael Ewers, Gloria Biechele, Marc Suárez-Calvet, Christian Sacher, Tanja Blume, Estrella Morenas-Rodriguez, Yuetiva Deming, Laura Piccio, Carlos Cruchaga, Gernot Kleinberger, Leslie Shaw, John Q. Trojanowski, Jochen Herms, Martin Dichgans, Matthias Brendel, Christian Haass, Nicolai Franzmeier

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

Abstract

Microglia activation is the brain's major immune response to amyloid plaques in Alzheimer's disease (AD). Both cerebrospinal fluid (CSF) levels of soluble TREM2 (sTREM2), a biomarker of microglia activation, and microglia PET are increased in AD; however, whether an increase in these biomarkers is associated with reduced amyloid-beta (Aβ) accumulation remains unclear. To address this question, we pursued a two-pronged translational approach. Firstly, in non-demented and demented individuals, we tested CSF sTREM2 at baseline to predict (i) amyloid PET changes over ∼2 years and (ii) tau PET cross-sectionally assessed in a subset of patients. We found higher CSF sTREM2 associated with attenuated amyloid PET increase and lower tau PET. Secondly, in the AppNL-G-F mouse model of amyloidosis, we studied baseline 18F-GE180 microglia PET and longitudinal amyloid PET to test the microglia vs. Aβ association, without any confounding co-pathologies often present in AD patients. Higher microglia PET at age 5 months was associated with a slower amyloid PET increase between ages 5-to-10 months. In conclusion, higher microglia activation as determined by CSF sTREM2 or microglia PET shows protective effects on subsequent amyloid accumulation.

Original languageEnglish
Article numbere12308
JournalEMBO Molecular Medicine
Volume12
Issue number9
DOIs
StatePublished - Sep 7 2020

Keywords

  • TREM2
  • beta-amyloid accumulation
  • microglia
  • protective
  • tau

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