NMR-based site-resolved profiling of β-amyloid misfolding reveals structural transitions from pathologically relevant spherical oligomer to fibril.

ABSTRACT: Increasing evidence highlights the central role of neurotoxic oligomers of the 42-residue-long β-amyloid (Aβ42) in Alzheimer's disease (AD). However, very limited information is available on the structural transition from oligomer to fibril, particularly for pathologically relevant amyloids. To the best of our knowledge, we present here the first site-specific structural characterization of Aβ42 misfolding, from toxic oligomeric assembly yielding a similar conformation to an AD-associated Aβ42 oligomer, into a fibril. Transmission EM (TEM) analysis revealed that a spherical amyloid assembly (SPA) of Aβ42 with a 15.6 ± 2.1-nm diameter forms in a ∼30-μm Aβ42 solution after a ∼10-h incubation at 4 °C, followed by a slow conversion into fibril at ∼180 h. Immunological analysis suggested that t

SUBMITTER: Xiao Y 

PROVIDER: S-EPMC6956526 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature