Sensitivity-Enhanced Solid-State NMR Detection of Structural Differences and Unique Polymorphs in Pico- to Nanomolar Amounts of Brain-Derived and Synthetic 42-Residue Amyloid-β Fibrils.

ABSTRACT: Amyloid-β (Aβ) fibrils in neuritic plaques are a hallmark of Alzheimer's disease (AD). Since the 42-residue Aβ (Aβ42) fibril is the most pathogenic among different Aβ species, its structural characterization is crucial to our understanding of AD. While several polymorphs have been reported for Aβ40, previous studies of Aβ42 fibrils prepared at neutral pH detected essentially only one structure, with an S-shaped β-sheet arrangement (e.g., Xiao et al. Nat. Struct. Mol. Biol. 2015, 22, 499). Herein, we demonstrate the feasibility of characterizing the structure of trace amounts of brain-derived and synthetic amyloid fibrils by sensitivity-enhanced ¹H-detected solid-state NMR (SSNMR) under ultrafast magic angle spinning. By taking advantage of the high sensitivity of t

SUBMITTER: Wickramasinghe A 

PROVIDER: S-EPMC10279877 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature