Abstract
Abrupt aggregation of amyloid beta (Aβ) peptide is strongly associated with Alzheimer's disease. In this study, we used atomic force microscopy-infrared (AFM-IR) spectroscopy to characterize the secondary structure of Aβ oligomers, protofibrils and fibrils formed at the early (4 h), middle (24 h), and late (72 h) stages of protein aggregation. This innovative spectroscopic approach allows for label-free nanoscale structural characterization of individual protein aggregates. Using AFM-IR, we found that at the early stage of protein aggregation, oligomers with parallel β-sheet dominated. However, these species exhibited slower rates of fibril formation compared to the oligomers with antiparallel β-sheet, which first appeared in the middle stage. These antiparallel β-sheet oligomers rapidly propagated into fibrils that were simultaneously observed together with parallel β-sheet fibrils at the late stage of protein aggregation. Our findings showed that aggregation of Aβ is a complex process that yields several distinctly different aggregates with dissimilar toxicities.