Analytical Validation of Tau and P-Tau as acute and subacute prognostic biomarkers for complicated mild TBI

与神经系统疾病候选生物标志物的分析验证的愿景一致 疾病PAR，我们组建了一个多学科的团队，并建议进行分析验证的两个 新出现的TBI生物标志物：Tau和磷酸化Tau（P-Tau）。尽管最近FDA批准了一对标记物 （神经元细胞体标志物UCH-L1和星形胶质细胞损伤标志物GFAP）诊断颅内CT异常， 然而，到目前为止，对于轻度TBI患者，还没有合格和有效的生物标志物直接与轴突损伤相关。 退行性轴索损伤和TBI后，尤其是TBU后的急性期和亚急性期。新兴 文献证据和我们自己数据指出基于血液的Tau/P-Tau水平可以填补这些未满足的生物标志物 需求我们提出了两种类型的Tau/ P-Tau使用背景（COU），作为复杂性高血压的预后生物标志物。 轻度TBI患者存在持续脑震荡后症状超过3个月的风险。虽然Tau/ P- Tau是有希望的TBI预后生物标志物，关于Tau/P-Tau存在显著的知识缺口 生物标志物，以及它们的检测分析。在这项拟议的研究中，我们将（1）创建Tau和P-Tau金 用于Tau/P-Tau平台测试的标准品和合并的阳性/阴性对照样品，以及 标准化，（2）在两个分析温度下评估Tau/P-Tau的新测定平台的分析性能 （3）建立不同年龄成人正常对照的Tau和P-Tau基线水平 （4）提供急性/亚急性Tau和P-Tau水平作为基于血液的生物标志物的支持性数据， （5）建立不同严重程度TBI患者血Tau、P-Tau水平的时间曲线 和损伤类型，最后（6）组装Tau/P-Tau TBI生物标志物鉴定计划，以提交给FDA 生物标志物鉴定程序。

Consistent with the vision of the Analytical Validation of a Candidate Biomarker for Neurological Disease PAR, we assembled a multidisciplinary team and propose to conduct analytical validation of two emerging TBI biomarkers: Tau and phospho-Tau (P-Tau). Although recently FDA approved a pair of markers (neuronal cell body marker UCH-L1 and astroglia injury marker GFAP) to diagnose cranial CT abnormality in mild TBI patients, however, to date, there are no qualified and validated biomarkers linked directly to axonal degenerative axonal injury and after TBI, especially in the acute and subacute phases after TBU. Emerging literature evidence and our own data point to blood-based Tau/P-Tau levels can fill these unmet biomarker needs. We propose two types of context of use (COU) for Tau/ P-Tau as prognostic biomarkers for complicated mild TBI patients at risk for persistent post-concussive symptoms lasting more than 3 months. While Tau/ P- Tau are promising TBI prognostic biomarkers, there are significant knowledge gaps regarding Tau/P-Tau biomarkers, as well as their detection assays. In this proposed study, we will (1) create Tau and P-Tau gold standards and pooled positive/negative controls samples for use in Tau/P-Tau platform testing and standardization, (2) assess the analytical performance of new assay platforms for Tau/P-Tau at two analytical sites, (3) establish the baseline blood levels of Tau and P-Tau in normative controls of different adult age intervals, (4) provide supportive data for acute/subacute Tau and P-Tau levels as blood-based biomarker for the indicated COU, (5) establish the temporal profile of blood Tau, P-Tau levels in TBI patients of varying severity and injury types, and lastly (6) assemble Tau/P-Tau TBI biomarker qualification plan for submission to FDA's Biomarker Qualification Program.