Ewers, MichaelBiechele, GloriaSuárez-Calvet, MarcSacher, ChristianBlume, TanjaMorenas-Rodriguez, EstrellaDeming, YuetivaPiccio, LauraCruchaga, CarlosKleinberger, GernotShaw, LeslieTrojanowski, John Q.Herms, JochenDichgans, MartinAlzheimer’s Disease Neuroimaging InitiativeBrendel, MatthiasHaass, ChristianFranzmeier, Nicolai2021-06-212021-06-212020Ewers M, Biechele G, Suárez-Calvet M, Sacher C, Blume T, Morenas-Rodriguez E, et al. Higher CSF sTREM2 and microglia activation are associated with slower rates of beta-amyloid accumulation. EMBO Mol Med. 2020 Sep 7; 12(9): e12308. DOI: 10.15252/emmm.2020123081757-4676http://hdl.handle.net/10230/47940Microglia 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 18 F-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.application/pdfengCopyright © 2020 The Authors. Published under the terms of the CC BY 4.0 license. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.info:eu-repo/semantics/articlehttp://dx.doi.org/10.15252/emmm.202012308TREM2Beta-amyloid accumulationMicrogliaProtectiveTauinfo:eu-repo/semantics/openAccess