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APOEε4 associates w...
APOEε4 associates with microglial activation independently of Aβ plaques and tau tangles
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Ferrari-Souza, J. P. (author)
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Lussier, F. Z. (author)
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Leffa, D. T. (author)
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Therriault, J. (author)
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Tissot, C. (author)
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Bellaver, B. (author)
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Ferreira, P. C. L. (author)
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Malpetti, M. (author)
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Wang, Y. T. (author)
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Povala, G. (author)
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- Lessa Benedet, Andréa (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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- Ashton, Nicholas J. (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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Chamoun, M. (author)
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Servaes, S. (author)
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Bezgin, G. (author)
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Kang, M. S. (author)
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Stevenson, J. (author)
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Rahmouni, N. (author)
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Pallen, V. (author)
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Poltronetti, N. M. (author)
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O'Brlen, J. T. (author)
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Rowe, J. B. (author)
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Cohen, A. D. (author)
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Lopez, O. L. (author)
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Tudorascu, D. L. (author)
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- Karikari, Thomas (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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Klunk, W. E. (author)
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Villemagne, V. L. (author)
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Soucy, J. P. (author)
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Gauthier, S. (author)
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Souza, D. O. (author)
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- Zetterberg, Henrik, 1973 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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- Blennow, Kaj, 1958 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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Zimmer, E. R. (author)
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Rosa-Neto, P. (author)
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Pascoal, T. A. (author)
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(creator_code:org_t)
- 2023
- 2023
- English.
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In: Science Advances. - 2375-2548. ; 9:14
- Related links:
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Subject headings
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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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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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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show more...
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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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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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Science Advances
- By the university
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University of Gothenburg