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APOEε4 associates with microglial activation independently of Aß plaques and tau tangles.
Ferrari-Souza, João Pedro; Lussier, Firoza Z; Leffa, Douglas T; Therriault, Joseph; Tissot, Cécile; Bellaver, Bruna; Ferreira, Pâmela C L; Malpetti, Maura; Wang, Yi-Ting; Povala, Guilherme; Benedet, Andréa L; Ashton, Nicholas J; Chamoun, Mira; Servaes, Stijn; Bezgin, Gleb; Kang, Min Su; Stevenson, Jenna; Rahmouni, Nesrine; Pallen, Vanessa; Poltronetti, Nina Margherita; O'Brien, John T; Rowe, James B; Cohen, Ann D; Lopez, Oscar L; Tudorascu, Dana L; Karikari, Thomas K; Klunk, William E; Villemagne, Victor L; Soucy, Jean-Paul; Gauthier, Serge; Souza, Diogo O; Zetterberg, Henrik; Blennow, Kaj; Zimmer, Eduardo R; Rosa-Neto, Pedro; Pascoal, Tharick A.
Afiliação
  • Ferrari-Souza JP; Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
  • Lussier FZ; Graduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
  • Leffa DT; Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
  • Therriault J; Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal; Department of Neurology and Neurosur
  • Tissot C; Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
  • Bellaver B; ADHD Outpatient Program and Development Psychiatry Program, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
  • Ferreira PCL; Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal; Department of Neurology and Neurosur
  • Malpetti M; Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
  • Wang YT; Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal; Department of Neurology and Neurosur
  • Povala G; Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
  • Benedet AL; Graduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
  • Ashton NJ; Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
  • Chamoun M; Department of Clinical Neurosciences, Cambridge University Hospitals NHS Trust, University of Cambridge, Cambridge, UK.
  • Servaes S; Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal; Department of Neurology and Neurosur
  • Bezgin G; Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
  • Kang MS; Graduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
  • Stevenson J; Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal; Department of Neurology and Neurosur
  • Rahmouni N; Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
  • Pallen V; Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
  • Poltronetti NM; Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.
  • O'Brien JT; Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
  • Rowe JB; Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal; Department of Neurology and Neurosur
  • Cohen AD; Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal; Department of Neurology and Neurosur
  • Lopez OL; Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal; Department of Neurology and Neurosur
  • Tudorascu DL; Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
  • Karikari TK; Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal; Department of Neurology and Neurosur
  • Klunk WE; Artificial Intelligence and Computational Neurosciences lab, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada.
  • Villemagne VL; LC Campbell Cognitive Neurology Unit, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada.
  • Soucy JP; Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal; Department of Neurology and Neurosur
  • Gauthier S; Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal; Department of Neurology and Neurosur
  • Souza DO; Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal; Department of Neurology and Neurosur
  • Zetterberg H; Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal; Department of Neurology and Neurosur
  • Blennow K; Department of Clinical Neurosciences, Cambridge University Hospitals NHS Trust, University of Cambridge, Cambridge, UK.
  • Zimmer ER; Department of Psychiatry, University of Cambridge, Cambridge, UK.
  • Rosa-Neto P; Department of Clinical Neurosciences, Cambridge University Hospitals NHS Trust, University of Cambridge, Cambridge, UK.
  • Pascoal TA; MRC Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, UK.
Sci Adv ; 9(14): eade1474, 2023 04 05.
Article em En | MEDLINE | ID: mdl-37018391
ABSTRACT
Animal 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-ß (Aß; [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 Aß and tau deposition. Furthermore, microglial activation mediated the Aß-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 Aß-independent effects on AD pathogenesis by activating microglia in brain regions associated with early tau deposition.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Microglia / Doença de Alzheimer Tipo de estudo: Risk_factors_studies Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Microglia / Doença de Alzheimer Tipo de estudo: Risk_factors_studies Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article