The microtubule nexus linking amyloid beta and tau: A simple and unifying theory for the underlying cause of Alzheimer's Disease

Alzheimers disease (AD) is defined by cognitive decline in conjunction with accumulation of aggregated amyloid {beta} (A{beta}) and tau, yet existing models of AD fail to provide a simple connection between A{beta} and tau. However, microtubules provide an intriguing nexus for pathological interactions between the two. Tau binds to microtubules and is critical to maintain their proper function. We demonstrate that A{beta} also binds to microtubules with affinity comparable that of tau itself. We hypothesize that displacement of tau by A{beta} leads to microtubule dysfunction and facilitates tau phosphorylation and aggregation. Importantly, in this model, aggregation of A{beta} is not the primary cause of toxicity, which allows many of the apparent contradictions between A{beta} pathology and cognition to be rationalized. This new model highlights the importance of both tau and A{beta} and enables novel therapeutic and intervention strategies to be considered.