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dc.contributor.authorSouza, João Pedro Ferraript_BR
dc.contributor.authorSouza, Diogo Onofre Gomes dept_BR
dc.contributor.authorZimmer, Eduardo Rigonpt_BR
dc.contributor.authorPascoal, Tharick Alipt_BR
dc.date.accessioned2023-06-17T03:37:44Zpt_BR
dc.date.issued2023pt_BR
dc.identifier.issn2375-2548pt_BR
dc.identifier.urihttp://hdl.handle.net/10183/259123pt_BR
dc.description.abstractAnimal studies suggest that the apolipoprotein E ε4 (APOEε4) allele is a culprit of early microglial activation in Alzheimer’s disease (AD). Here, we tested the association between APOEε4 status and microglial activation in living individuals across the aging and AD spectrum. We studied 118 individuals with positron emission tomography for amyloid-β (Aβ; [18F]AZD4694), tau ([18F]MK6240), and microglial activation ([11C]PBR28). We found that APOEε4 carriers presented increased microglial activation relative to noncarriers in early Braak stage regions within the medial temporal cortex accounting for Aβ and tau deposition. Furthermore, microglial activation mediated the Aβ-independent effects of APOEε4 on tau accumulation, which was further associated with neurodegeneration and clinical impairment. The physiological distribution of APOE mRNA expression predicted the patterns of APOEε4-related microglial activation in our population, suggesting that APOE gene expression may regulate the local vulnerability to neuroinflammation. Our results support that the APOEε4 genotype exerts Aβ-independent effects on AD pathogenesis by activating microglia in brain regions associated with early tau deposition.en
dc.format.mimetypeapplication/pdfpt_BR
dc.language.isoengpt_BR
dc.relation.ispartofScience advances. Washington, DC. Vol. 9, no. 14 (Apr. 2023), eade 1474, 10 p.pt_BR
dc.rightsOpen Accessen
dc.subjectDoenças neurodegenerativaspt_BR
dc.subjectDoença de Alzheimerpt_BR
dc.subjectApolipoproteína E4pt_BR
dc.subjectMicrogliapt_BR
dc.titleAPOEε4 associates with microglial activation independently of Aβ plaques and tau tanglespt_BR
dc.typeArtigo de periódicopt_BR
dc.identifier.nrb001167743pt_BR
dc.type.originEstrangeiropt_BR


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