Department of Neurology and Psychiatry, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, United States.
Handb Clin Neurol. 2023;196:251-265. doi: 10.1016/B978-0-323-98817-9.00015-6.
Tauopathies are a clinically and neuropathologically heterogeneous group of neurodegenerative disorders, characterized by abnormal tau aggregates. Tau, a microtubule-associated protein, is important for cytoskeletal structure and intracellular transport. Aberrant posttranslational modification of tau results in abnormal tau aggregates causing neurodegeneration. Tauopathies may be primary, or secondary, where a second protein, such as Aß, is necessary for pathology, for example, in Alzheimer's disease, the most common tauopathy. Primary tauopathies are classified based on tau isoform and cell types where pathology predominates. Primary tauopathies include Pick disease, corticobasal degeneration, progressive supranuclear palsy, and argyrophilic grain disease. Environmental tauopathies include chronic traumatic encephalopathy and geographically isolated tauopathies such as the Guam-Parkinsonian-dementia complex. The clinical presentation of tauopathies varies based on the brain areas affected, generally presenting with a combination of cognitive and motor symptoms either earlier or later in the disease course. As symptoms overlap and tauopathies such as Alzheimer's disease and argyrophilic grain disease often coexist, accurate clinical diagnosis is challenging when biomarkers are unavailable. Available treatments target cognitive, motor, and behavioral symptoms. Disease-modifying therapies have been the focus of drug development, particularly agents targeting Aß and tau pathology in Alzheimer's disease, although most of these trials have failed.
tau 病是一组临床上和神经病理学上具有异质性的神经退行性疾病，其特征是异常的 tau 聚集物。tau 是一种微管相关蛋白，对于细胞骨架结构和细胞内运输很重要。tau 的异常翻译后修饰导致异常 tau 聚集物引起神经退行性变。tau 病可能是原发性的，也可能是继发性的，需要第二种蛋白质（如 Aβ）才能发生病理学改变，例如在阿尔茨海默病（最常见的 tau 病）中。原发性 tau 病基于 tau 异构体和主要发生病变的细胞类型进行分类。原发性 tau 病包括匹克病、皮质基底节变性、进行性核上性麻痹和嗜银颗粒病。环境 tau 病包括慢性创伤性脑病和地理隔离性 tau 病，如关岛帕金森病痴呆综合征。tau 病的临床表现因受影响的脑区而异，通常在疾病过程的早期或晚期出现认知和运动症状的组合。由于症状重叠，且 tau 病（如阿尔茨海默病和嗜银颗粒病）常同时存在，当缺乏生物标志物时，准确的临床诊断具有挑战性。现有的治疗方法针对认知、运动和行为症状。疾病修饰疗法一直是药物开发的重点，特别是针对阿尔茨海默病中 Aβ和 tau 病理学的药物，尽管这些试验大多失败了。
