Exogenous amyloidogenic proteins function as seeds in amyloid β-protein aggregation

Amyloid beta-protein (A beta) aggregation is considered to be a critical step in the neurodegeneration of Alzheimer's disease (AD). In addition to A beta, many proteins aggregate into the amyloid state, in which they form elongated fibers with spines comprising stranded beta-sheets. However, the cross-seeding effects of other protein aggregates on A beta aggregation pathways are not completely clear. To investigate the cross-seeding effects of exogenous and human non-CNS amyloidogenic proteins on A beta aggregation pathways, we examined whether and how sonicated fibrils of casein, fibroin, sericin, actin, and islet amyloid polypeptide affected A beta 40 and A beta 42 aggregation pathways using the thioflavin T assay and electron microscopy. Interestingly, the fibrillar seeds of all amyloidogenic proteins functioned as seeds. The cross-seeding effect of actin was stronger but that of fibroin was weaker than that of other proteins. Furthermore, our nuclear magnetic resonance spectroscopic studies identified the binding sites of A beta with the amyloidogenic proteins. Our results indicate that the amyloidogenic proteins, including those contained in foods and cosmetics, contribute to A beta aggregation by binding to A beta, suggesting their possible roles in the propagation of A beta amyloidosis. (C) 2014 Elsevier B.V. All rights reserved.