Cryo-EM of amyloid fibrils and cellular aggregates

Neurodegenerative and other protein misfolding diseases are associated with the aggregation of a protein, which may be mutated in genetic forms of disease, or the wild type form in late onset sporadic disease. A wide variety of proteins and peptides can be involved, with aggregation originating from a natively folded or a natively unstructured species. Large deposits of amyloid fibrils are typically associated with cell death in late stage pathology. In this review, we illustrate the contributions of cryo-EM and related methods to the structure determination of amyloid fibrils extracted post mortem from patient brains or formed in vitro. We also discuss cell models of protein aggregation and the contributions of electron tomography to understanding the cellular context of aggregation.