Animal models of tauopathies and their implications for research/translation into the clinic

Our aims are to review animal models of tauopathies, which include a number of brain disorders with various aetiologies, including ageing, genetics, infectious diseases, toxins, trauma and other unknown factors. Tauopathies are characterized by the accumulation of filaments of the microtubule-associated tau protein. The different aetiopathogeneses and distinct molecular events involved in tau aggregation have led to the development of various animal models for these diseases. In this review, rather than listing all current models, we focus on specific animal models addressing, among others, the question of tau hyperphosphorylation, tau aggregation and tau spreading. Physiological conditions, including normal ageing and hibernation, may exhibit tau phosphorylation and some aspects of tauopathies. However, most of the models of tauopathies involve genetically modified animals (mostly rodents, but also fruit fly, zebrafish and worm). Some of these models have been crucial for the development of therapeutic approaches in humans. The present review shows the difficulty in pinpointing a specific mechanism that may be targeted in tauopathies but also opens up new avenues for innovative therapeutic strategies.