Tau neurotoxicity and rescue in animal models of human Tauopathies

•Soluble species of Tau, rather than aggregates, are more detrimental to proper neuronal function.•Tau is released from synaptic terminals into the extracellular space.•Tau plays a role in controlling susceptibility to hyperexcitation.•Tau based antibody or aggregation inhibitor treatment is beneficial in murine Tauopathy models.

Pathological Tau is a hallmark of various neuronal disorders and spreads in the brain of Alzheimer patients in a well-defined manner. Beside Tau's main function in stabilizing microtubules for axonal transport, a variety of novel functions for neurons and glia have emerged recently. Tau regulates the susceptibility to hyperexcitation and plays a role in neuron-glia contact formation. Studies implicate soluble oligomeric species of Tau, rather than insoluble aggregates, as more detrimental to proper neuronal function. Tau is not exclusively intracellular; instead Tau can be released into the extracellular space. This has led to the hypothesis of a prion-disease like mechanism to explain the stereotypical progression of Tau. Targeting pathological Tau with antibodies or aggregation inhibitors may help to prevent pathology.