Astrocytes contain amyloid-β annular protofibrils in Alzheimer's disease brains

Cristian A. Lasagna-Reeves, Rakez Kayed

    Research output: Contribution to journalArticlepeer-review

    33 Scopus citations

    Abstract

    Annular protofibrils (APFs) represent a newly described and distinct class of amyloid structures formed by disease-associated proteins. In vitro, these pore-like structures have been implicated in membrane permeabilization and ion homeostasis via pore formation. Still, their formation and relevance in vivo are poorly understood. Herein, we report that APFs are in human Alzheimer's disease brain samples and that amyloid-β APFs were associated with activated astrocytes. Moreover, we show that amyloid-β APFs in astrocytes adopt a conformation in which the N-terminal region is buried inside the wall of the pore. Our results together with previous studies suggest that the formation of amyloid-β APFs in astrocytes could be a relevant event in the pathogenesis of Alzheimer's disease and validate this amyloidogenic structure as a target for the prevention of the disease.

    Original languageEnglish (US)
    Pages (from-to)3052-3057
    Number of pages6
    JournalFEBS Letters
    Volume585
    Issue number19
    DOIs
    StatePublished - Oct 3 2011

    Keywords

    • Alzheimer disease
    • Amyloid-β peptide
    • Annular protofibril
    • Astrocyte

    ASJC Scopus subject areas

    • Biophysics
    • Structural Biology
    • Biochemistry
    • Molecular Biology
    • Genetics
    • Cell Biology

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