Department of Neurology, Geriatrics Research Institute and Hospital, Maebashi, Japan.
Adv Exp Med Biol. 2019;1184:393-405. doi: 10.1007/978-981-32-9358-8_29.
Cerebrospinal fluid (CSF) tau and phosphorylated tau (ptau) are definite biomarkers of Alzheimer's disease (AD). After discovery of presence and increased levels tau in CSF from AD patients using specific ELISA, numerous reports revealed that CSF levels of tau are increased in AD and brain injury, phosphorylated tau are specifically increased in AD. Many large cohort studies also confirmed that natural course of CSF tau and ptau levels initiated from cognitively unimpaired AD stage after longstanding progress of brain Aß amyloidosis. Close correlation with neuroimaging findings of Tau PET and with deterioration of cognitive function domains have been elucidated. CSF tau also increase in neurodegeneration and acute brain injury. Global standardization, assay technology inventions, and research of tau kinetics from brain synthesis and clearance into CSF are developing. Trace amount of plasma p-tau assay are also validated. Development of these studies provide that CSF tau is the biomarker of CNS neurodegeneration and CSF ptau is the specific biomarker of CNS tauopathy. Assays of CSF and plasma tau and ptau are essential tools not only for prediction and diagnosis of AD and but for newly developing disease modified therapies of AD.
脑脊液(CSF)中的 tau 和磷酸化 tau(ptau)是阿尔茨海默病(AD)的明确生物标志物。在使用特定 ELISA 从 AD 患者的 CSF 中发现 tau 的存在和水平增加后,许多报告显示 AD 和脑损伤患者的 CSF 中 tau 水平增加,ptau 则特异性增加 AD。许多大型队列研究还证实,CSF tau 和 ptau 水平的自然病程始于认知无损害的 AD 阶段,之后是脑 Aβ淀粉样变性的长期进展。与 Tau PET 的神经影像学发现以及认知功能域的恶化密切相关。CSF tau 也会在神经退行性变和急性脑损伤中增加。CSF 中 tau 从脑合成和清除到 CSF 的动力学的全球标准化、检测技术发明和研究正在发展。痕量血浆 p-tau 检测也得到了验证。这些研究的发展表明,CSF tau 是中枢神经系统神经退行性变的生物标志物,CSF ptau 是中枢神经系统 tau 病的特异性生物标志物。CSF 和血浆 tau 和 ptau 的检测不仅是 AD 预测和诊断的必要工具,也是 AD 新型疾病修饰治疗的必要工具。