Tau-based therapies in neurodegeneration: opportunities and challenges.

Aggregates of the microtubule-associated protein tau are a defining feature of several neurodegenerative diseases that are collectively known as tauopathies, and constitute one of the hallmark lesions of Alzheimer disease (AD). Given the lack of efficacy to date of amyloid-β-targeted therapies for AD, interest is growing in tau as a potential alternative target. Several drug candidates, which are now in clinical trials, aim to reduce tau levels or to prevent the aggregation or pathological post-translation modifications of this protein. In this Review, we discuss preclinical and clinical studies in light of an increased understanding of the physiological and pathological roles of tau, advances in animal models of tauopathy, the identification of novel targets and the availability of novel tracers to track tau.