Taken together, this body of work supports the idea that therapies that modulate tau levels or function have the potential to lead to clinically meaningful benefits in slowing or reversing disease progression. Increasingly, human clinical trials are testing this hypothesis. This article aims to review the potential tau pathological mechanisms in neurodegenerative disease, and the current tau-directed therapeutic agents that have reached the clinical phase of development. In primary tauopathies, tau is an obvious target given the evidence of its direct cause of the disease. It is also clear that the tau is an attractive target in secondary tauopathies such as AD, and the failure of multiple phase III clinical trials in Alzheimer's disease (AD) with drugs targeting Aβ has fueled increasing interest in alternative therapeutic approaches, especially those targeting tau pathology. Given that tau pathology is a better correlate with cognitive impairments than Aβ plaques, targeting tau can be more effective than Aβ clearance.
