Cross-seeding effects of amyloid β-protein and α-synuclein

J. Neurochem. (2012) 122, 883890. Abstract Amyloid beta-protein (A beta) and a-synuclein (aS) are the primary components of amyloid plaques and Lewy bodies (LBs), respectively. Previous in vitro and in vivo studies have suggested that interactions between A beta and aS are involved in the pathogenesis of Alzheimers disease and LB diseases. However, the seeding effects of their aggregates on their aggregation pathways are not completely clear. To investigate the cross-seeding effects of A beta and aS, we examined how sonicated fibrils or cross-linked oligomers of A beta 40, A beta 42, and aS affected their aggregation pathways using thioflavin T(S) assay and electron microscopy. Fibrils and oligomers of A beta 40, A beta 42, and aS acted as seeds, and affected the aggregation pathways within and among species. The seeding effects of aS fibrils were higher than those of A beta 40 and A beta 42 fibrils in the A beta 40 and A beta 42 aggregation pathways, respectively. We showed that A beta and aS acted as seeds and affected each others aggregation pathways in vitro, which may contribute to our understanding of the molecular mechanisms of interactions between Alzheimers disease and LB diseases pathologies.