Assessing the causes and consequences of co-polymerization in amyloid formation

How, and why, different proteins form amyloid fibrils is most often studied in vitro using a single purified protein sequence. However, many amyloid diseases involve co-aggregation of different protein species, including proteins with/without post-translational modifications (e.g., different strains of PrP), proteins of different length (e.g., β2-microglobulin and ΔN6, Aβ40, and Aβ42), sequence variants (e.g., Aβ and AβARC), and proteins from different organisms (e.g., bovine PrP and human PrP). The consequences of coaggregation of different proteins upon the structure, stability, species transmission and toxicity of the resulting amyloid aggregates is discussed here, including the role of co-aggregation in expanding the repertoire of oligomeric and fibrillar structures and how this can affect their biological and biophysical properties.