Application of EPR spectroscopy in the structural studies of Aβ oligomers and fibrils

Electron paramagnetic resonance (EPR) spectroscopy, in combination with site-directed spin labeling, is a powerful tool to elucidate the structures of Aβ oligomers and fibrils central to Alzheimer's disease pathology. This chapter describes general strategies of spin labeling, sample preparation, and data analysis for EPR studies of Aβ aggregation. The parallel in-register β-sheet structure commonly found in many amyloid fibrils gives rise to a characteristic single-line EPR spectrum. Quantitative analysis of the single-line spectrum reveals site-specific structural information in both Aβ fibrils and oligomers. In addition to structural studies, EPR methods for mechanistic studies such as co-aggregation and oligomer-to-fibril conversion are also discussed. This chapter underscores the important role of EPR in providing structural and mechanistic insights into Aβ aggregation with implications for a better molecular understanding of Alzheimer's disease.