Tau pathology refers to molecular mechanisms leading to the intracellular aggregation of abnormally modified Tau protein isoforms and to the propagation of this degenerating process along neuronal �circuitry. Tau proteins belong to the family of microtubule-associated proteins. Tau is strongly expressed in neurons, localized in the axon and is essential for neuronal architecture, plasticity and network. In animal models, overexpression of mutated Tau proteins is often used to induce a Tau pathology, leading to motor and/or cognitive dysfunction. These animal models are essential to understand how neuronal degeneration and Tau aggregation are related. Indeed, Tau pathology is certainly a good therapeutic target, but untangling Tau remains a major therapeutic challenge.