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

与神经病学候选生物标记物的分析验证的愿景一致 疾病标准，我们组建了一个多学科团队，并建议对两个 新出现的脑损伤生物标志物：Tau和磷酸Tau(P-Tau)。尽管最近FDA批准了一对标志物 神经元体标记UCH-L1和星形胶质细胞损伤标记GFAP对颅脑CT异常的诊断价值 然而，到目前为止，还没有与轴突直接相关的合格和有效的生物标志物。 退行性轴索损伤和脑损伤后，尤其是脑损伤后的急性期和亚急性期。新兴 文献证据和我们自己的数据表明，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 需要。我们提出了两种Tau/P-Tau的使用环境(COU)作为复杂疾病的预后生物标志物 轻度颅脑损伤患者有持续脑震荡后症状持续3个月以上的风险。而Tau/P- Tau是很有前景的脑损伤预后生物标志物，目前对Tau/P-Tau的认识还存在很大差距 生物标志物及其检测分析。在这项拟议的研究中，我们将(1)创建Tau和P-Tau黄金 用于Tau/P-Tau平台测试的标准和混合阳性/阴性对照样品 标准化，(2)评估新的Tau/P-Tau分析平台的分析性能 (3)建立不同年龄段正常对照的Tau和P-Tau基线水平 间隔，(4)提供急性/亚急性Tau和P-Tau水平的支持性数据，作为基于血液的生物标志物 (5)建立不同程度颅脑损伤患者血中Tau、P-Tau水平的时间分布 和损伤类型，最后(6)编制Tau/P-Tau TBI生物标记物鉴定计划，提交给FDA 生物标记物资格认证计划。

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.