Phosphorylation is one of the most prevalent post-translational modifications found in aggregated tau isolated from Alzheimer’s disease (AD) patient brains. In tauopathies like AD, increased phosphorylation or hyperphosphorylation can contribute to microtubule dysfunction and is associated with tau aggregation. In this review, we provide an overview of the structure and functions of tau protein as well as the physiologic roles of tau phosphorylation. We also extensively survey tau phosphorylation sites identified in brain tissue and cerebrospinal fluid from AD patients compared to age-matched healthy controls, which may serve as disease-specific biomarkers. Recently, new assays have been developed to measure minute amounts of specific forms of phosphorylated tau in both cerebrospinal fluid and plasma, which could potentially be useful for aiding clinical diagnosis and monitoring disease progression. Additionally, multiple therapies targeting phosphorylated tau are in various stages of clinical trials including kinase inhibitors, phosphatase activators, and tau immunotherapy. With promising early results, therapies that target phosphorylated tau could be useful at slowing tau hyperphosphorylation and aggregation in AD and other tauopathies.

中文翻译：

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“不要对 Tau 进行磷酸化”：针对阿尔茨海默病和其他 tau 蛋白病的 tau 蛋白磷酸化的临床生物标志物和疗法的最新进展

磷酸化是在从阿尔茨海默病 (AD) 患者大脑中分离的聚合 tau 中发现的最普遍的翻译后修饰之一。在 AD 等 tau 蛋白病中，磷酸化增加或过度磷酸化可导致微管功能障碍，并与 tau 聚集有关。在这篇综述中，我们概述了 tau 蛋白的结构和功能以及 tau 磷酸化的生理作用。我们还广泛调查了 AD 患者脑组织和脑脊液中发现的 tau 磷酸化位点与年龄匹配的健康对照相比，这可能作为疾病特异性生物标志物。最近，已经开发出新的检测方法来测量脑脊液和血浆中微量的特定形式的磷酸化 tau，这可能有助于临床诊断和监测疾病进展。此外，针对磷酸化 tau 的多种疗法正处于临床试验的不同阶段，包括激酶抑制剂、磷酸酶激活剂和 tau 免疫疗法。凭借有希望的早期结果，靶向磷酸化 tau 的疗法可用于减缓 AD 和其他 tau 病变中的 tau 过度磷酸化和聚集。