title: Acceleration of amyloid fibril formation by specific binding of Abeta-(1-40) peptide to ganglioside-containing membrane vesicles.
abstract: The interaction of Alzheimer's Abeta peptide and its fluorescent analogue with membrane vesicles was studied by spectrofluorometry, Congo Red binding, and electron microscopy. The peptide binds selectively to the membranes containing gangliosides with a binding affinity ranging from 10(-6) to 10(-7) M depending on the type of ganglioside sugar moiety. This interaction appears to be ganglioside-specific as under our experimental conditions (neutral pH, physiologically relevant ionic strength), no Abeta binding was observed to ganglioside-free membranes containing zwitterionic or acidic phospholipids. Importantly, the addition of ganglioside-containing vesicles to the peptide solution dramatically accelerates the rate of fibril formation as compared with that of the peptide alone. The present results strongly suggest that the membrane-bound form of the peptide may act as a specific "template" (seed) that catalyzes the fibrillogenesis process in vivo.
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: L P
authors.initials: LP
authors.lastname: Choo-Smith
authors.forename: W
authors.initials: W
authors.lastname: Garzon-Rodriguez
authors.forename: C G
authors.initials: CG
authors.lastname: Glabe
authors.forename: W K
authors.initials: WK
authors.lastname: Surewicz
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology / Q000473:pathology; D000682:Amyloid / Q000378:metabolism* / Q000648:ultrastructure*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D003224:Congo Red; D005456:Fluorescent Dyes; D005732:Gangliosides / Q000378:metabolism*; D006801:Humans; D008081:Liposomes / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D013050:Spectrometry, Fluorescence
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D005456:Fluorescent Dyes; D005732:Gangliosides; D008081:Liposomes; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D003224:Congo Red