Structural evolution of Iowa mutant β-amyloid fibrils from polymorphic to homogeneous states under repeated seeded growth.

ABSTRACT: Structural variations in β-amyloid fibrils are potentially important to the toxicity of these fibrils in Alzheimer's disease (AD). We describe a repeated seeding protocol that selects a homogeneous fibril structure from a polymorphic initial state in the case of 40-residue β-amyloid fibrils with the Asp23-to-Asn, or Iowa, mutation (D23N-Aβ(1-40)). We use thioflavin T (ThT) fluorescence, transmission electron microscopy (TEM), and solid-state nuclear magnetic resonance (NMR) to track the evolution of fibril structure through multiple generations under this protocol. The data show that (i) repeated seeding selectively amplifies a single D23N-Aβ(1-40) fibril structure that can be a minor component of the initial polymorphic state; (ii) the final structure is highly sensitive to growth conditi

SUBMITTER: Qiang W 

PROVIDER: S-EPMC3060308 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature