Cross-seeding between Aβ40 and Aβ42 in Alzheimer's disease

A beta 42 is the major component of parenchymal plaques in the brain of Alzheimer's patients, while A beta 40 is the major component of cerebrovascular plaques. Since A beta 40 and A beta 42 coexist in the brain, understanding the interaction between A beta 40 and A beta 42 during their aggregation is important to delineate the molecular mechanism underlying Alzheimer's disease. Here, we present a rigorous and systematic study of the cross-seeding effects between A beta 40 and A beta 42. We show that A beta 40 fibril seeds can promote A beta 42 aggregation in a concentration-dependent manner, and vice versa. Our results also suggest that seeded aggregation and spontaneous aggregation may be two separate pathways. These findings may partly resolve conflicting observations in the literature regarding the cross-seeding effects between A beta 40 and A beta 42.