Nanoscale Hyperspectral Imaging of Amyloid Secondary Structures in Liquid

Abnormal aggregation of amyloid-beta is a very complex and heterogeneous process. Owing to methodological limitations, the aggregation pathway is still not fully understood. Herein a new approach is presented in which the secondary structure of single amyloid-beta aggregates is investigated with tip-enhanced Raman spectroscopy (TERS) in a liquid environment. Clearly resolved TERS signatures of the amide I and amide III bands enabled a detailed analysis of the molecular structure of single aggregates at each phase of the primary aggregation of amyloid-beta and also of small species on the surface of fibrils attributed to secondary nucleation. Notably, a beta-sheet rearrangement from antiparallel in protofibrils to parallel in fibrils is observed. This study allows better understanding of Alzheimer's disease etiology and the methodology can be applied in studies of other neurodegenerative disorders.

Automated summary

Abnormal aggregation of amyloid-beta is a complex and heterogeneous process, and a new approach using TERS has provided detailed molecular structure information of single amyloid-beta aggregates, revealing a beta-sheet rearrangement. This study will contribute to a better understanding of the etiology of Alzheimer's disease.