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APOEε4 associates w...
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Ferrari-Souza, J. P.
(author)
APOEε4 associates with microglial activation independently of Aβ plaques and tau tangles
- Article/chapterEnglish2023
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LIBRIS-ID:oai:gup.ub.gu.se/327949
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https://gup.ub.gu.se/publication/327949URI
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https://doi.org/10.1126/sciadv.ade1474DOI
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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Animal studies suggest that the apolipoprotein E epsilon 4 (APOE epsilon 4) allele is a culprit of early microglial activation in Alzheimer's disease (AD). Here, we tested the association between APOE epsilon 4 status and microglial activation in living individuals across the aging and AD spectrum. We studied 118 individuals with positron emission tomog-raphy for amyloid-beta (A beta; [18F]AZD4694), tau ([18F]MK6240), and microglial activation ([11C]PBR28). We found that APOE epsilon 4 carriers presented increased microglial activation relative to noncarriers in early Braak stage regions within the medial temporal cortex accounting for A beta and tau deposition. Furthermore, microglial acti-vation mediated the A beta-independent effects of APOE epsilon 4 on tau accumulation, which was further associated with neurodegeneration and clinical impairment. The physiological distribution of APOE mRNA expression predicted the patterns of APOE epsilon 4-related microglial activation in our population, suggesting that APOE gene expression may regulate the local vulnerability to neuroinflammation. Our results support that the APOE epsilon 4 genotype exerts A beta-independent effects on AD pathogenesis by activating microglia in brain regions associated with early tau deposition.
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Lussier, F. Z.
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Leffa, D. T.
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Therriault, J.
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Tissot, C.
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Bellaver, B.
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Ferreira, P. C. L.
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Malpetti, M.
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Wang, Y. T.
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Povala, G.
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Lessa Benedet, AndréaGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xlesan
(author)
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Ashton, Nicholas J.Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xashtn
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Chamoun, M.
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Servaes, S.
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Bezgin, G.
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Kang, M. S.
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Stevenson, J.
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Rahmouni, N.
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Pallen, V.
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Poltronetti, N. M.
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O'Brlen, J. T.
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Rowe, J. B.
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Cohen, A. D.
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Lopez, O. L.
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Tudorascu, D. L.
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Karikari, ThomasGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xkarit
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Klunk, W. E.
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Villemagne, V. L.
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Soucy, J. P.
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Gauthier, S.
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Souza, D. O.
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Zetterberg, Henrik,1973Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xzethe
(author)
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Blennow, Kaj,1958Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xbleka
(author)
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Zimmer, E. R.
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Rosa-Neto, P.
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Pascoal, T. A.
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Göteborgs universitetInstitutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi
(creator_code:org_t)
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In:Science Advances9:142375-2548
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Ferrari-Souza, J ...
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Lussier, F. Z.
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Leffa, D. T.
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Therriault, J.
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Tissot, C.
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Bellaver, B.
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Ferreira, P. C. ...
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Malpetti, M.
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Wang, Y. T.
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Povala, G.
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Lessa Benedet, A ...
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Ashton, Nicholas ...
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Chamoun, M.
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Servaes, S.
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Bezgin, G.
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Kang, M. S.
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Stevenson, J.
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Rahmouni, N.
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Pallen, V.
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Poltronetti, N. ...
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O'Brlen, J. T.
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Rowe, J. B.
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Cohen, A. D.
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Lopez, O. L.
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Tudorascu, D. L.
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Karikari, Thomas
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Klunk, W. E.
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Villemagne, V. L ...
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Soucy, J. P.
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Gauthier, S.
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Souza, D. O.
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Zetterberg, Henr ...
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Blennow, Kaj, 19 ...
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Zimmer, E. R.
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Rosa-Neto, P.
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Pascoal, T. A.
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Neurosciences
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Science Advances
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University of Gothenburg