title: In situ Abeta pores in AD brain are cylindrical assembly of Abeta protofilaments.
abstract: According to the amyloid pore hypothesis, pores formed by small oligomers of misfolded amyloidogenic proteins cause membrane leakage with the unregulated rapid influx of ions leading to cell death. Ultrastructurally, pores reconstituted in vitro have mainly been characterised so far, and the presence of in situ pores in the amyloid tissues has not yet been demonstrated. In this study, the presence of in situbeta amyloid (Abeta) pores was shown with high resolution transmission electron microscopy, in the neuronal cell membrane as well as in the membrane of mitochondria-like organelles in the brain with Alzheimer's disease. They are 16 nm wide and 11 nm long flat columnar structures made up of a single cylindrical layer (wall) of laterally associated Abeta protofilaments which surrounds a 10 nm wide opening or lumen. Protofilaments are the basic unit of the fibrils of all amyloid-forming proteins and peptides. Individual extracellular Abeta protofilaments were 2-3 nm wide straight tubular structures with helical wall formed by the tight coiling of 1 nm wide Abeta filaments. These in situ Abeta pores are similar but not identical to in vitro reconstituted Abeta pores.
authors.affiliation: Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada. sadayuki.inoue@mcgill.ca
authors.forename: Sadayuki
authors.initials: S
authors.lastname: Inoue
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D001921:Brain / Q000378:metabolism* / Q000648:ultrastructure; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D006801:Humans; D008297:Male; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D008954:Models, Biological; D058225:Plaque, Amyloid / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D016229:Amyloid beta-Peptides