Accelerated Alzheimer's Aβ-42 secondary nucleation chronologically visualized on fibril surfaces.

ABSTRACT: Protein fibril surfaces tend to generate toxic oligomers catalytically. To date, efforts to study the accelerated aggregation steps involved with Alzheimer's disease-linked amyloid-β (Aβ)-42 proteins on fibril surfaces have mainly relied on fluorophore-based analytics. Here, we visualize rare secondary nucleation events on the surface of Aβ-42 fibrils from embryonic to endpoint stages using liquid-based atomic force microscopy. Nanoscale imaging supported by atomic-scale molecular simulations tracked the adsorption and proliferation of oligomeric assemblies at nonperiodically spaced catalytic sites on the fibril surface. Upon confirming that fibril edges are preferential binding sites for oligomers during embryonic stages, the secondary fibrillar size changes were quantified during the gro

SUBMITTER: Nirmalraj PN 

PROVIDER: S-EPMC11506133 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature