title: ABri peptide associated with familial British dementia forms annular and ring-like protofibrillar structures.
abstract: Amyloid plaque deposition involves the aggregation of normally soluble proteins into insoluble amyloid fibrils (fibrillization) and proceeds through intermediates with distinct morphologies, including spherical aggregates, protofibrils, and mature fibrils. Recently, a novel annular protofibril-like intermediate with unique pore-like properties was produced by alpha-synuclein, A beta-Arctic and amylin, which are proteins associated with Parkinson's disease, Alzheimer's disease, and type-II diabetes. The observation of annular structures coupled with size selective channel-like activity by these proteins suggests that these structures may be responsible for vesicle permeability by ion-channel formation. Using atomic force spectroscopy, we report here that the ABri peptide associated with familial British dementia produces similar annular and ring-like protofibril structures during the following sequence of events: spherical aggregates (0.4-1.5 nm height)-->chain-like protofibrils (1.5-2.3 nm height)-->ring-like protofibrils and annular protofibrils (1.5-2.3 nm height). This suggests that ABri fibrillization occurs in a similar fashion to other amyloidogenic proteins and that the annular protofibrillar structures may represent a common amyloid intermediate.
authors.affiliation: Department of Chemistry, Case Western Reserve University, Cleveland, Ohio 44106-7078, USA.
authors.forename: Rekha
authors.initials: R
authors.lastname: Srinivasan
authors.forename: Roger E
authors.initials: RE
authors.lastname: Marchant
authors.forename: Michael G
authors.initials: MG
authors.lastname: Zagorski
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D000682:Amyloid / Q000737:chemistry / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D006801:Humans; D058228:Islet Amyloid Polypeptide; D018625:Microscopy, Atomic Force; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D058225:Plaque, Amyloid / Q000378:metabolism; D051843:Synucleins; D051844:alpha-Synuclein
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D058228:Islet Amyloid Polypeptide; D009419:Nerve Tissue Proteins; D010455:Peptides; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein