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.
Original language | English |
---|---|
Journal | ChemBioChem |
Pages (from-to) | 3521-3524 |
Number of pages | 5 |
ISSN | 1439-4227 |
DOIs | |
Publication status | Published - 2020 |