Synergistic Interactions between Repeats in Tau Protein and Aβ Amyloids May Be Responsible for Accelerated Aggregation via Polymorphic States

Amyloid plaques and neurofibrillary tangles simultaneously accumulate in Alzheimer's disease (AD). It is known that A beta and tau exist together in the mitochondria; however, the interactions between A beta oligomers and tau are controversial. Moreover, it is still unclear which specific domains in the tau protein can interact with A beta oligomers and what could be the effect of these interactions. Herein, we examine three different A beta-tau oligomeric complexes. These complexes present interactions of A beta with three domains in the tau protein; all contain high beta-structure propensity in their R2, R3, and R4 repeats. Our results show that, among these, A beta oligomers are likely to interact with the R2 domain to form a stable complex with better alignment in the turn region and the beta-structure domain. We therefore propose that the R2 domain can interact with soluble A beta oligomers and consequently promote aggregation. EM and AFM images and dimensions revealed highly polymorphic tau aggregates. We suggest that the polymorphic tau and A beta-tau aggregates may be largely due to repeat sequences which are prone to variable turn locations along the tau repeats.