sTREM2 is associated with amyloid-related p-tau increases and glucose hypermetabolism in Alzheimer's disease

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• dc.contributor.author Biel, Davina
• dc.contributor.author Suárez-Calvet, Marc
• dc.contributor.author Hager, Paul
• dc.contributor.author Rubinski, Annna
• dc.contributor.author Dewenter Anna
• dc.contributor.author Steward, Anna
• dc.contributor.author Roemer, Sebastian
• dc.contributor.author Ewers, Michael
• dc.contributor.author Haass, Christian
• dc.contributor.author Brendel, Matthias
• dc.contributor.author Franzmeier, Nicolai
• dc.contributor.author Alzheimer’s Disease Neuroimaging Initiative
• dc.date.accessioned 2024-02-12T08:03:13Z
• dc.date.available 2024-02-12T08:03:13Z
• dc.date.issued 2023
• dc.description.abstract Microglial activation occurs early in Alzheimer's disease (AD) and previous studies reported both detrimental and protective effects of microglia on AD progression. Here, we used CSF sTREM2 to investigate disease stage‐dependent drivers of microglial activation and to determine downstream consequences on AD progression. We included 402 patients with measures of earliest beta‐amyloid (CSF Aβ1‐42) and late‐stage fibrillary Aβ pathology (amyloid‐PET centiloid), as well as sTREM2, p‐tau181, and FDG‐PET. To determine disease stage, we stratified participants into early Aβ‐accumulators (Aβ CSF+/PET−; n = 70) or late Aβ‐accumulators (Aβ CSF+/PET+; n = 201) plus 131 controls. In early Aβ‐accumulators, higher centiloid was associated with cross‐sectional/longitudinal sTREM2 and p‐tau181 increases. Further, higher sTREM2 mediated the association between centiloid and cross‐sectional/longitudinal p‐tau181 increases and higher sTREM2 was associated with FDG‐PET hypermetabolism. In late Aβ‐accumulators, we found no association between centiloid and sTREM2 but a cross‐sectional association between higher sTREM2, higher p‐tau181 and glucose hypometabolism. Our findings suggest that a TREM2‐related microglial response follows earliest Aβ fibrillization, manifests in inflammatory glucose hypermetabolism and may facilitate subsequent p‐tau181 increases in earliest AD.
• dc.description.sponsorship The study was funded by grants from the LMU (FöFoLe,1032, awarded to NF;FöFoLe,1119, awarded to DB), the Hertie foundation for clinical neurosciences(awarded to NF), and the SyNergy excellence cluster (EXC2145/ID390857198).MSC receives funding from the European Research Council (ERC) under theEuropean Union’s Horizon2020research and innovation programme (Grantagreement No.948677), the Instituto de Salud Carlos III (PI19/00155), and froma fellowship from“la Caixa”Foundation (ID100010434) and from theEuropean Union’s Horizon2020research and innovation programme underthe Marie Skłodowska-Curie grant agreement No.847648(LCF/BQ/PR21/11840004). We thank the ADNI participants and their families who made thisstudy possible. Open Access funding enabled and organized by Projekt DEAL.
• dc.format.mimetype application/pdf
• dc.identifier.citation Biel D, Suárez-Calvet M, Hager P, Rubinski A, Dewenter A, Steward A, et al. sTREM2 is associated with amyloid-related p-tau increases and glucose hypermetabolism in Alzheimer's disease. EMBO Mol Med. 2023 Feb 8;15(2):e16987. DOI: 10.15252/emmm.202216987
• dc.identifier.doi http://dx.doi.org/10.15252/emmm.202216987
• dc.identifier.issn 1757-4676
• dc.identifier.uri http://hdl.handle.net/10230/59075
• dc.language.iso eng
• dc.publisher EMBO Press
• dc.relation.ispartof EMBO Mol Med. 2023 Feb 8;15(2):e16987
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/948677
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/847648
• dc.rights © 2023 The Authors. Published under the terms of the CC BY 4.0 license.This is an open access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), 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 Alzheimer's disease
• dc.subject.keyword Beta-amyloid
• dc.subject.keyword Glucose metabolism
• dc.subject.keyword P-tau
• dc.subject.keyword sTREM2
• dc.title sTREM2 is associated with amyloid-related p-tau increases and glucose hypermetabolism in Alzheimer's disease
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion