Abstract
Protein aggregation is a complex process, consisting of a large number of pathways connecting monomers and mature amyloid fibrils. Recent advances in structure determination techniques, such as solid-state NMR and cryoEM, have allowed the determination of atomic resolution structures of fibril polymorphs, but most of the intermediate stages of the process including oligomer formation remain unknown. Proper characterization of the heterogeneity of the process is critical not only for physical and chemical understanding of the aggregation process but also for elucidation of the disease mechanisms and identification of therapeutic targets. This article reviews recent developments in the characterization of heterogeneity in amyloid formation processes.