Beta Amyloid Peptide:Research Paper: Probing the secondary structure of individual Aβ40 amorphous aggregates and fibrils by AFM-IR spectroscopy

Probing the secondary structure of individual Aβ40 amorphous aggregates and fibrils by AFM-IR spectroscopy

Abstract

Structural characterization of aggregates and fibrils of the Aβ protein is pivotal to the molecular level elucidation of Alzheimer's disease (AD). AFM-IR provides nanoscale resolution, and thus allows for spectroscopic interrogation of individual aggregates and fibrils. During aggregation of Aβ we observed mainly disordered Aβ at t=15 min, substantial structural diversity including co-existence of parallel and antiparallel β-sheets within a large amorphous aggregate at t=2 hours, while fibrils exhibited the expected signature of parallel β-sheets at t=1 week. The resonance observed for parallel β-sheets at t=2 hours coincides with that observed for fibrils (at 1634 cm-1), indicating that fibril-like species exist within the large aggregates. Thus, nucleation might occur within such species, in analogy to current theories of protein crystallization where nucleation occurs within large protein clusters. Cu2+ perturbs Aβ aggregation, catalysing rapid formation of amorphous aggregates with diverse secondary structure, but inhibiting fibril growth.

Keywords: AFM-IR; Aβ40; Cu2+; Nucleation; Protein Aggregation.

© 2020 Wiley-VCH GmbH.

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