Synapse-binding subpopulations of Aβ oligomers sensitive to peptide assembly blockers and scFv antibodies.

ABSTRACT: Amyloid β42 self-assembly is complex, with multiple pathways leading to large insoluble fibrils or soluble oligomers. Oligomers are now regarded as most germane to Alzheimer's pathogenesis. We have investigated the hypothesis that oligomer formation itself occurs through alternative pathways, with some leading to synapse-binding toxins. Immediately after adding synthetic peptide to buffer, solutions of Aβ42 were separated by a 50 kDa filter and fractions assessed by SDS-PAGE silver stain, Western blot, immunoprecipitation, and capacity for synaptic binding. Aβ42 rapidly assembled into aqueous-stable oligomers, with similar protein abundance in small (<50 kDa) and large (>50 kDa) oligomer fractions. Initially, both fractions were SDS-labile and resolved into tetramers, trimers, and monomers

SUBMITTER: Velasco PT 

PROVIDER: S-EPMC3503444 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature