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  • Bellaver, B. (author)

Astrocyte reactivity influences amyloid-beta effects on tau pathology in preclinical Alzheimer's disease

  • Article/chapterEnglish2023

Publisher, publication year, extent ...

  • 2023

Numbers

  • LIBRIS-ID:oai:gup.ub.gu.se/329944
  • https://gup.ub.gu.se/publication/329944URI
  • https://doi.org/10.1038/s41591-023-02380-xDOI

Supplementary language notes

  • Language:English

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

Notes

  • Cross-sectional and longitudinal analyses of tau pathology in preclinical Alzheimer's disease reveal that tau tangles accumulate as a function of amyloid-beta burden only in individuals positive for an astrocyte reactivity biomarker. An unresolved question for the understanding of Alzheimer's disease (AD) pathophysiology is why a significant percentage of amyloid-beta (A beta)-positive cognitively unimpaired (CU) individuals do not develop detectable downstream tau pathology and, consequently, clinical deterioration. In vitro evidence suggests that reactive astrocytes unleash A beta effects in pathological tau phosphorylation. Here, in a biomarker study across three cohorts (n = 1,016), we tested whether astrocyte reactivity modulates the association of A beta with tau phosphorylation in CU individuals. We found that A beta was associated with increased plasma phosphorylated tau only in individuals positive for astrocyte reactivity (Ast(+)). Cross-sectional and longitudinal tau-positron emission tomography analyses revealed an AD-like pattern of tau tangle accumulation as a function of A beta only in CU Ast(+) individuals. Our findings suggest astrocyte reactivity as an important upstream event linking A beta with initial tau pathology, which may have implications for the biological definition of preclinical AD and for selecting CU individuals for clinical trials.

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  • Povala, G. (author)
  • Ferreira, P. C. L. (author)
  • Ferrari-Souza, J. P. (author)
  • Leffa, D. T. (author)
  • Lussier, F. Z. (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)
  • Triana-Baltzer, G. (author)
  • Kolb, H. C. (author)
  • Tissot, C. (author)
  • Therriault, J. (author)
  • Servaes, S. (author)
  • Stevenson, J. (author)
  • Rahmouni, N. (author)
  • Lopez, O. L. (author)
  • Tudorascu, D. L. (author)
  • Villemagne, V. L. (author)
  • Ikonomovic, M. D. (author)
  • Gauthier, S. (author)
  • Zimmer, E. R. (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)
  • Aizenstein, H. J. (author)
  • Klunk, W. E. (author)
  • Snitz, B. E. (author)
  • Maki, P. (author)
  • Thurston, R. C. (author)
  • Cohen, A. D. (author)
  • Ganguli, M. (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)
  • 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:Nature Medicine29:71078-8956

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