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.