Diverse Structural Conversion and Aggregation Pathways of Alzheimer's Amyloid-β (1-40).

ABSTRACT: Complex amyloid aggregation of amyloid-β (1-40) (Aβ_1-40) in terms of monomer structures has not been fully understood. Herein, we report the microscopic mechanism and pathways of Aβ_1-40 aggregation with macroscopic viewpoints through tuning its initial structure and solubility. Partial helical structures of Aβ_1-40 induced by low solvent polarity accelerated cytotoxic Aβ_1-40 amyloid fibrillation, while predominantly helical folds did not aggregate. Changes in the solvent polarity caused a rapid formation of β-structure-rich protofibrils or oligomers via aggregation-prone helical structures. Modulation of the pH and salt concentration transformed oligomers to protofibrils, which proceeded to amyloid formation. We reveal diverse molecular mec

SUBMITTER: Lin Y 

PROVIDER: S-EPMC11585080 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature