Nanoscale Characterization of Parallel and Antiparallel -Sheet Amyloid Beta 1-42 Aggregates.

abstract

• Abrupt aggregation of amyloid beta (A) 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 A 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 -sheet dominated. However, these species exhibited slower rates of fibril formation compared to the oligomers with antiparallel -sheet, which first appeared in the middle stage. These antiparallel -sheet oligomers rapidly propagated into fibrils that were simultaneously observed together with parallel -sheet fibrils at the late stage of protein aggregation. Our findings showed that aggregation of A is a complex process that yields several distinctly different aggregates with dissimilar toxicities.

authors

• Kurouski, Dzmitry

published proceedings

• ACS Chem Neurosci

altmetric score

• 11.6

author list (cited authors)

• Zhaliazka, K., & Kurouski, D.

citation count

• 7

publication date

• October 2022

publisher

• American Chemical Society (ACS)  Publisher

keywords

• Alzheimer’s Disease
• Amyloid
• Amyloid Beta-Peptides
• Amyloid β1−42
• Atomic Force Microscopy
• Fibrils
• Infrared Spectroscopy
• Microscopy, Atomic Force
• Oligomers
• Protein Aggregates
• Protein Conformation, Beta-strand
• Protein Structure, Secondary

Digital Object Identifier (DOI)

• 10.1021/acschemneuro.2c00180

start page

• 2813

end page

• 2820

volume

• 13

issue

• 19

URL

• http://dx.doi.org/10.1021/acschemneuro.2c00180