Initial stages of beta-amyloid Aβ_1-40 and Aβ_1-42 oligomerization observed using fluorescence decay and molecular...

The development of Alzheimer's disease is associated with the aggregation of the beta-amyloid peptides Aβ_1-40 and Aβ_1-42. It is believed that the small oligomers formed during the early stages of the aggregation are neurotoxic and involved in the process of neurodegeneration. In this paper we use fluorescence decay measurements of beta-amyloid intrinsic fluorophore tyrosine (Tyr) and molecular dynamics (MD) simulations to study the early stages of oligomer formation for the Aβ_1-40 and Aβ_1-42 peptides in vitro. We demonstrate that the lifetime distributions of the amyloid fluorescence decay efficiently describe changes in the complex Tyr photophysics during the peptide aggregation and highlight the differences in aggregation performance of the two amyloids. Tyr fluorescence decay is found to be a more sensitive sensor of Aβ_1-40 aggregation than Aβ_1-42 aggregation. The MD simulation of the peptide aggregation is compared with the experimental data and supports a four-rotamer model of Tyr.