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.

微管相关蛋白tau的聚集体是几种神经退行性疾病（定义为tauopathies）的定义特征，构成阿尔茨海默病（AD）的标志性病变之一。鉴于迄今缺乏针对Aβ的淀粉样蛋白靶向疗法的疗效，人们对tau作为潜在的替代靶点的兴趣日益浓厚。目前正在临床试验中的几种候选药物旨在降低tau含量或防止这种蛋白质的聚集或病理性的翻译后修饰。在这篇综述中，我们将根据对tau的生理和病理作用的进一步了解，tauopathy的动物模型的进展，新靶标的鉴定以及追踪tau的新型示踪剂的可用性来讨论临床前和临床研究。