title: Amyloid-β annular protofibrils evade fibrillar fate in Alzheimer disease brain.
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.
authors.affiliation: Department of Neurology, George P. and Cynthia Woods Mitchell Center for Neurodegenerative Diseases, University of Texas Medical Branch, Galveston, Texas 77555-1045, USA.
authors.forename: Cristian A
authors.initials: CA
authors.lastname: Lasagna-Reeves
authors.forename: Charles G
authors.initials: CG
authors.lastname: Glabe
authors.forename: Rakez
authors.initials: R
authors.lastname: Kayed
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D058225:Plaque, Amyloid / Q000378:metabolism; D016062:Porosity; D055503:Protein Multimerization; D017433:Protein Structure, Secondary
chemical_list: D016229:Amyloid beta-Peptides