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Astrocyte reactivit...
Astrocyte reactivity influences amyloid-beta effects on tau pathology in preclinical Alzheimer's disease
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Bellaver, B. (author)
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Povala, G. (author)
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Ferreira, P. C. L. (author)
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Ferrari-Souza, J. P. (author)
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Leffa, D. T. (author)
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Lussier, F. Z. (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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Triana-Baltzer, G. (author)
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Kolb, H. C. (author)
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Tissot, C. (author)
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Therriault, J. (author)
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Servaes, S. (author)
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Stevenson, J. (author)
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Rahmouni, N. (author)
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Lopez, O. L. (author)
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Tudorascu, D. L. (author)
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Villemagne, V. L. (author)
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Ikonomovic, M. D. (author)
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Gauthier, S. (author)
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Zimmer, E. R. (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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Aizenstein, H. J. (author)
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Klunk, W. E. (author)
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Snitz, B. E. (author)
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Maki, P. (author)
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Thurston, R. C. (author)
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Cohen, A. D. (author)
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Ganguli, M. (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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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: Nature Medicine. - 1078-8956. ; 29:7
- 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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- 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.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Bellaver, B.
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Povala, G.
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Ferreira, P. C. ...
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Ferrari-Souza, J ...
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Leffa, D. T.
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Lussier, F. Z.
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show more...
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Lessa Benedet, A ...
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Ashton, Nicholas ...
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Triana-Baltzer, ...
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Kolb, H. C.
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Tissot, C.
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Therriault, J.
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Servaes, S.
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Stevenson, J.
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Rahmouni, N.
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Lopez, O. L.
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Tudorascu, D. L.
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Villemagne, V. L ...
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Ikonomovic, M. D ...
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Gauthier, S.
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Zimmer, E. R.
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Zetterberg, Henr ...
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Blennow, Kaj, 19 ...
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Aizenstein, H. J ...
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Klunk, W. E.
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Snitz, B. E.
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Maki, P.
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Thurston, R. C.
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Cohen, A. D.
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Ganguli, M.
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Karikari, Thomas
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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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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
- Articles in the publication
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Nature Medicine
- By the university
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University of Gothenburg