Observation of β-Amyloid Peptide Oligomerization by Pressure-Jump NMR Spectroscopy.

ABSTRACT: Brain tissue of Alzheimer's disease patients invariably contains deposits of insoluble, fibrillar aggregates of peptide fragments of the amyloid precursor protein (APP), typically 40 or 42 residues in length and referred to as Aβ⁴⁰ and Aβ⁴². However, it remains unclear whether these fibrils or oligomers constitute the toxic species. Depending on sample conditions, oligomers can form in a few seconds or less. These oligomers are invisible to solution NMR spectroscopy, but they can be rapidly (<1 s) resolubilized and converted to their NMR-visible monomeric constituents by raising the hydrostatic pressure to a few kbar. Hence, utilizing pressure-jump NMR, the oligomeric state can be studied at residue-specific resolution by monitoring its signals in the monomeric state.

SUBMITTER: Barnes CA 

PROVIDER: S-EPMC9357264 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature