Synergistic Interactions between Repeats in Tau Protein and A beta 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.

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