Characterization of Homogeneous and Heterogeneous Amyloid-β42 Oligomer Preparations with Biochemical Methods and Infrared Spectroscopy Reveals a Correlation between Infrared Spectrum and Oligomer Size

Soluble oligomers of the amyloid-beta(1-42) (A beta 42) peptide, widely considered to be among the relevant neurotoxic species involved in Alzheimer's disease, were characterized with a combination of biochemical and biophysical methods. Homogeneous and stable A beta 42 oligomers were prepared by treating monomeric solutions of the peptide with detergents. The prepared oligomeric solutions were analyzed with blue native and sodium dodecyl sulfate polyacrylamide gel electrophoresis, as well as with infrared (IR) spectroscopy. The IR spectra indicated a well-defined beta-sheet structure of the prepared oligomers. We also found a relationship between the size/molecular weight of the A beta 42 oligomers and their IR spectra: The position of the main amide I' band of the peptide backbone correlated with oligomer size, with larger oligomers being associated with lower wavenumbers. This relationship explained the time-dependent band shift observed in time-resolved IR studies of A beta 42 aggregation in the absence of detergents, during which the oligomer size increased. In addition, the bandwidth of the main IR band in the amide I' region was found to become narrower with time in our time-resolved aggregation experiments, indicating a more homogeneous absorption of the beta-sheets of the oligomers after several hours of aggregation. This is predominantly due to the consumption of smaller oligomers in the aggregation process.

Automated summary

Soluble oligomers of the amyloid-beta(1-42) peptide, which are considered neurotoxic in Alzheimer's disease, were characterized using biochemical and biophysical methods. The size of the oligomers was found to correlate with the position of the main amide I' band in the IR spectra, with larger oligomers having lower wavenumbers. Time-resolved aggregation experiments showed a more homogeneous absorption of beta-sheets in the oligomers after several hours, due to the consumption of smaller oligomers.