Tau is mainly an intracellular protein, however in recent years there is growing evidence that tau is found in the extracellular space under physiological conditions. [83,84] It has been proposed that tau is regulated by neuronal activity and that extracellular tau may play a role in regulating synaptic function and excitability. Studies from animal and cellular models suggest that pathogenic tau can propagate between neighboring brain cells or synaptically connected neurons following a prion-like spreading mechanism [85-87]. It is hypothesized that tau species with seeding capability can be transmitted from cell-to-cell and recruit soluble tau into growing aggregates, and that this process may play a critical role in the pathogenesis of tau and the neurodegenerative process.
