Propagation of an Aβ Dodecamer Strain Involves a Three-Step Mechanism and a Key Intermediate.

ABSTRACT: Proteinaceous deposits composed of fibrillar amyloid-β (Aβ) are the primary neuropathological hallmarks in Alzheimer disease (AD) brains. The nucleation-dependent aggregation of Aβ is a stochastic process with frequently observed heterogeneity in aggregate size, structure, and conformation that manifests in fibril polymorphism. Emerging evidence indicates that polymorphic variations in Aβ fibrils contribute to phenotypic diversity and the rate of disease progression in AD. We recently demonstrated that a dodecamer strain derived from synthetic Aβ42 propagates to morphologically distinct fibrils and selectively induces cerebral amyloid angiopathy phenotype in transgenic mice. This report supports the growing contention that stable oligomer strains can influence phenotypic outcomes by faithf

SUBMITTER: Dean DN 

PROVIDER: S-EPMC5985009 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature