Amyloid-β annular protofibrils evade fibrillar fate in Alzheimer disease brain

Cristian A. Lasagna-Reeves, Charles G. Glabe, Rakez Kayed

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

Annular protofibrils (APFs) represent a new 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, evidence for their formation and relevance in vivo is lacking. Herein, we report that APFs are in a distinct pathway from fibril formation in vitro and in vivo. In human Alzheimer disease brain samples, amyloid-β APFs were associated with diffuse plaques, but not compact plaques; moreover, we show the formation of intracellular APFs. Our results together with previous studies suggest that the prevention of amyloid-β annular protofibril formation could be a relevant target for the prevention of amyloid-β toxicity in Alzheimer disease.

Original languageEnglish (US)
Pages (from-to)22122-22130
Number of pages9
JournalJournal of Biological Chemistry
Volume286
Issue number25
DOIs
StatePublished - Jun 24 2011

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Amyloid
Brain
Alzheimer Disease
Toxicity
Homeostasis
Ions
Membranes
Proteins
In Vitro Techniques

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Amyloid-β annular protofibrils evade fibrillar fate in Alzheimer disease brain. / Lasagna-Reeves, Cristian A.; Glabe, Charles G.; Kayed, Rakez.

In: Journal of Biological Chemistry, Vol. 286, No. 25, 24.06.2011, p. 22122-22130.

Research output: Contribution to journalArticle

Lasagna-Reeves, Cristian A. ; Glabe, Charles G. ; Kayed, Rakez. / Amyloid-β annular protofibrils evade fibrillar fate in Alzheimer disease brain. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 25. pp. 22122-22130.
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