Wallenberg Centre for Molecular and Translational Medicine and the Department of Psychiatry and Neurochemistry, University of Gothenburg, Gothenburg, Sweden; Clinical Memory Research Unit, Lund University, Malmö, Sweden; Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
German Center for Neurodegenerative Diseases, Magdeburg, Germany; Helen Wills Neuroscience Institute, University of California, Berkeley, USA.
Mol Cell Neurosci. 2019 Jun;97:18-33. doi: 10.1016/j.mcn.2018.12.001. Epub 2018 Dec 7.
The aggregation of fibrils of hyperphosphorylated and C-terminally truncated microtubule-associated tau protein characterizes 80% of all dementia disorders, the most common neurodegenerative disorders. These so-called tauopathies are hitherto not curable and their diagnosis, especially at early disease stages, has traditionally proven difficult. A keystone in the diagnosis of tauopathies was the development of methods to assess levels of tau protein in vivo in cerebrospinal fluid, which has significantly improved our knowledge about these conditions. Tau proteins have also been measured in blood, but the importance of tau-related changes in blood is still unclear. The recent addition of positron emission tomography ligands to visualize, map and quantify tau pathology has further contributed with information about the temporal and spatial characteristics of tau accumulation in the living brain. Together, the measurement of tau with fluid biomarkers and positron emission tomography constitutes the basis for a highly active field of research. This review describes the current state of biomarkers for tau biomarkers derived from neuroimaging and from the analysis of bodily fluids and their roles in the detection, diagnosis and prognosis of tau-associated neurodegenerative disorders, as well as their associations with neuropathological findings, and aims to provide a perspective on how these biomarkers might be employed prospectively in research and clinical settings.
过度磷酸化和 C 端截断的微管相关 tau 蛋白纤丝的聚集是所有痴呆症(最常见的神经退行性疾病)的 80%的特征。这些所谓的 tau 病至今无法治愈,其诊断,尤其是在早期疾病阶段,传统上一直难以进行。tau 病诊断的一个关键是开发评估脑脊液中 tau 蛋白水平的方法,这大大提高了我们对这些疾病的认识。tau 蛋白也在血液中进行了测量,但 tau 相关变化在血液中的重要性仍不清楚。最近,正电子发射断层扫描配体的加入有助于可视化、映射和量化 tau 病理学,进一步提供了关于 tau 在活体大脑中积累的时间和空间特征的信息。总之,使用液体生物标志物和正电子发射断层扫描来测量 tau 构成了一个高度活跃的研究领域的基础。这篇综述描述了源自神经影像学和体液分析的 tau 生物标志物的当前状态,以及它们在 tau 相关神经退行性疾病的检测、诊断和预后中的作用,以及它们与神经病理学发现的关联,并旨在提供一个如何前瞻性地在研究和临床环境中使用这些生物标志物的视角。