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

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• dc.contributor.author Ewers, Michael
• dc.contributor.author Biechele, Gloria
• dc.contributor.author Suárez-Calvet, Marc
• dc.contributor.author Sacher, Christian
• dc.contributor.author Blume, Tanja
• dc.contributor.author Morenas-Rodriguez, Estrella
• dc.contributor.author Deming, Yuetiva
• dc.contributor.author Piccio, Laura
• dc.contributor.author Cruchaga, Carlos
• dc.contributor.author Kleinberger, Gernot
• dc.contributor.author Shaw, Leslie
• dc.contributor.author Trojanowski, John Q.
• dc.contributor.author Herms, Jochen
• dc.contributor.author Dichgans, Martin
• dc.contributor.author Alzheimer’s Disease Neuroimaging Initiative
• dc.contributor.author Brendel, Matthias
• dc.contributor.author Haass, Christian
• dc.contributor.author Franzmeier, Nicolai
• dc.date.accessioned 2021-06-21T07:45:05Z
• dc.date.available 2021-06-21T07:45:05Z
• dc.date.issued 2020
• dc.description.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 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.
• dc.format.mimetype application/pdf
• dc.identifier.citation Ewers 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.202012308
• dc.identifier.doi http://dx.doi.org/10.15252/emmm.202012308
• dc.identifier.issn 1757-4676
• dc.identifier.uri http://hdl.handle.net/10230/47940
• dc.language.iso eng
• dc.publisher Wiley
• dc.rights Copyright © 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.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword TREM2
• dc.subject.keyword Beta-amyloid accumulation
• dc.subject.keyword Microglia
• dc.subject.keyword Protective
• dc.subject.keyword Tau
• dc.title Higher CSF sTREM2 and microglia activation are associated with slower rates of beta-amyloid accumulation
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/acceptedVersion