Transforming growth factor-β1 potentiates amyloid-β generation in astrocytes and in transgenic mice

Sylvain Lesné, Fabian Docagne, Cecília Gabriel, Géraldine Liot, Debomoy K. Lahiri, Luc Buée, Laurent Plawinski, André Delacourte, Eric T. MacKenzie, Alain Buisson, Denis Vivien

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93 Scopus citations

Abstract

Accumulation of the amyloid-β peptide (Aβ) in the brain is crucial for development of Alzheimer's disease. Expression of transforming growth factor-β1 (TGF-β1), an immunosuppressive cytokine, has been correlated in vivo with Aβ accumulation in transgenic mice and recently with Aβ clearance by activated microglia. Here, we demonstrate that TGF-β1 drives the production of Aβ40/42 by astrocytes leading to Aβ production in TGF-β1 transgenic mice. First, TGF-β1 induces the overexpression of the amyloid precursor protein (APP) in astrocytes but not in neurons, involving a highly conserved TGF-β1-responsive element in the 5′-untranslated region (+54/+74) of the APP promoter. Second, we demonstrated an increased release of soluble APP-β which led to TGF-β1-induced Aβ generation in both murine and human astrocytes. These results demonstrate that TGF-β1 potentiates Aβ production in human astrocytes and may enhance the formation of plaques burden in the brain of Alzheimer's disease patients.

Original languageEnglish (US)
Pages (from-to)18408-18418
Number of pages11
JournalJournal of Biological Chemistry
Volume278
Issue number20
DOIs
StatePublished - May 16 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Lesné, S., Docagne, F., Gabriel, C., Liot, G., Lahiri, D. K., Buée, L., Plawinski, L., Delacourte, A., MacKenzie, E. T., Buisson, A., & Vivien, D. (2003). Transforming growth factor-β1 potentiates amyloid-β generation in astrocytes and in transgenic mice. Journal of Biological Chemistry, 278(20), 18408-18418. https://doi.org/10.1074/jbc.M300819200