title: High-speed atomic force microscopy reveals structural dynamics of amyloid β1-42 aggregates.
abstract: Aggregation of amyloidogenic proteins into insoluble amyloid fibrils is implicated in various neurodegenerative diseases. This process involves protein assembly into oligomeric intermediates and fibrils with highly polymorphic molecular structures. These structural differences may be responsible for different disease presentations. For this reason, elucidation of the structural features and assembly kinetics of amyloidogenic proteins has been an area of intense study. We report here the results of high-speed atomic force microscopy (HS-AFM) studies of fibril formation and elongation by the 42-residue form of the amyloid β-protein (Aβ1-42), a key pathogenetic agent of Alzheimer's disease. Our data demonstrate two different growth modes of Aβ1-42, one producing straight fibrils and the other producing spiral fibrils. Each mode depends on initial fibril nucleus structure, but switching from one growth mode to another was occasionally observed, suggesting that fibril end structure fluctuated between the two growth modes. This switching phenomenon was affected by buffer salt composition. Our findings indicate that polymorphism in fibril structure can occur after fibril nucleation and is affected by relatively modest changes in environmental conditions.
authors.affiliation: Bio-AFM Frontier Research Center, Kanazawa University, Kanazawa 920-1192, Japan;
authors.forename: Takahiro
authors.initials: T
authors.lastname: Watanabe-Nakayama
authors.affiliation: Department of Neurology and Neurobiology and Aging, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8640, Japan; Department of Neurology, Showa University School of Medicine, Tokyo 142-8666, Japan;
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Ono
authors.affiliation: Bio-AFM Frontier Research Center, Kanazawa University, Kanazawa 920-1192, Japan;
authors.forename: Masahiro
authors.initials: M
authors.lastname: Itami
authors.affiliation: Department of Neurology and Neurobiology and Aging, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8640, Japan;
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Takahashi
authors.affiliation: Department of Neurology, The University of California, Los Angeles School of Medicine, Los Angeles, CA 90095.
authors.forename: David B
authors.initials: DB
authors.lastname: Teplow
authors.affiliation: Department of Neurology and Neurobiology and Aging, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8640, Japan; m-yamada@med.kanazawa-u.ac.jp.
authors.forename: Masahito
authors.initials: M
authors.lastname: Yamada
mesh_terms: D000682:Amyloid / Q000737:chemistry / Q000648:ultrastructure*; D016229:Amyloid beta-Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D002021:Buffers; D006801:Humans; D018625:Microscopy, Atomic Force; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry*; D011189:Potassium Chloride / Q000737:chemistry; D011487:Protein Conformation; D012965:Sodium Chloride / Q000737:chemistry; D012996:Solutions; D013499:Surface Properties
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D002021:Buffers; D010446:Peptide Fragments; D012996:Solutions; C075222:amyloid beta-protein (1-42); D012965:Sodium Chloride; D011189:Potassium Chloride
keywords: Alzheimer's disease; amyloidogenic proteins; atomic force microscopy; kinetics