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APOEε4 associates with microglial activation independently of Aβ plaques and tau tangles

Ferrari-Souza, J. P. (author)
Lussier, F. Z. (author)
Leffa, D. T. (author)
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Therriault, J. (author)
Tissot, C. (author)
Bellaver, B. (author)
Ferreira, P. C. L. (author)
Malpetti, M. (author)
Wang, Y. T. (author)
Povala, G. (author)
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
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
Chamoun, M. (author)
Servaes, S. (author)
Bezgin, G. (author)
Kang, M. S. (author)
Stevenson, J. (author)
Rahmouni, N. (author)
Pallen, V. (author)
Poltronetti, N. M. (author)
O'Brlen, J. T. (author)
Rowe, J. B. (author)
Cohen, A. D. (author)
Lopez, O. L. (author)
Tudorascu, D. L. (author)
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
Klunk, W. E. (author)
Villemagne, V. L. (author)
Soucy, J. P. (author)
Gauthier, S. (author)
Souza, D. O. (author)
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
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
Zimmer, E. R. (author)
Rosa-Neto, P. (author)
Pascoal, T. A. (author)
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 (creator_code:org_t)
2023
2023
English.
In: Science Advances. - 2375-2548. ; 9:14
Related links:
https://gup.ub.gu.se...
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https://doi.org/10.1...
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  • Journal article (peer-reviewed)
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)

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