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  • Ferrari-Souza, J. P. (author)

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

  • Article/chapterEnglish2023

Publisher, publication year, extent ...

  • 2023

Numbers

  • LIBRIS-ID:oai:gup.ub.gu.se/327949
  • https://gup.ub.gu.se/publication/327949URI
  • https://doi.org/10.1126/sciadv.ade1474DOI

Supplementary language notes

  • Language:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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. (author)
  • Leffa, D. T. (author)
  • 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, 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)
  • 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 (author)
  • 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, 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 (author)
  • Klunk, W. E. (author)
  • Villemagne, V. L. (author)
  • Soucy, J. P. (author)
  • Gauthier, S. (author)
  • Souza, D. O. (author)
  • 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)
  • 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)
  • Zimmer, E. R. (author)
  • Rosa-Neto, P. (author)
  • Pascoal, T. A. (author)
  • Göteborgs universitetInstitutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi (creator_code:org_t)

Related titles

  • In:Science Advances9:142375-2548

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