Pathological tau interactors and their role in propagation and neurodegeneration

Tau aggregates are critical pathological features of Alzheimer’s disease (AD) and other tauopathies. An important focus of research has been to understand the pathological tau propagation in AD patient brains that follow neuronal networks. Despite the knowledge acquired, the cellular mechanism involved in tau propagation and seeding are still unclear. Unfortunately, the nature of the tau species involved in the spreading and the precise seeding/template remains unknown. Despite this uncertainty, some studies suggest that a high molecular weight tau (HMW‐tau) is the form of tau involved in trans‐synaptic propagation. It remains unresolved whether these HMW‐tau particles are made exclusively of tau or contain other constituents such as proteins necessary for propagation.