AUTHOR=Yadikar Hamad , Kobeissy Firas H. , Robertson Claudia , Tsetsou Spyridoula , Williamson John B. , Lamb Damon G. , Wagner Amy K. , Kibaugh Todd , Kao Shih-Han , Kou Zhifeng , Welch Robert D. , Yamal Jose-Miguel , Leon-Novelo Luis , Rubenstein Richard , Wang Kevin K. W. 

TITLE=Early cerebrospinal fluid elevations of pTau-217 in severe traumatic brain injury subjects

JOURNAL=Frontiers in Neurology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1632679

DOI=10.3389/fneur.2025.1632679

ISSN=1664-2295

ABSTRACT=IntroductionTauopathies, including Alzheimer’s disease (AD), feature abnormal accumulations of hyperphosphorylated Tau protein; however, their biomarker potential in traumatic brain injury (TBI) is not well-defined. This study investigated whether cerebrospinal fluid (CSF) phosphorylated Tau at threonine-217 (pTau-217) could serve as an early biomarker for severe TBI (sTBI).MethodsCSF samples from 26 sTBI patients, collected between 6 and 240 h post-injury, and 19 healthy controls were analyzed using an optimized direct enzyme-linked immunosorbent assay (ELISA; sensitivity <4.7 pg/mL) for pTau-217 detection, complemented by Western blot validation. Temporal analysis, ROC curves, and trajectory clustering were used for interpretation.ResultsCSF pTau-217 levels were significantly elevated in sTBI patients at 6, 12, 18, 24, and 48 h post-injury compared to controls (p < 0.05–p < 0.001), peaking around 18 h (~65 ng/mL) before declining to near-control levels by 120 h. ROC analyses showed AUC of 0.78 (6–12 h) and 0.83 (24–48 h). Clustering identified a subgroup with sustained high pTau-217, associated with diffuse axonal injury and worse 6-month outcomes. A significant inverse correlation was observed between CSF pTau-217 at 24–48 h and GOSE (ρ = –0.67, p < 0.01).DiscussionThese findings indicate that CSF pTau-217 is a sensitive and early biomarker of acute tau pathology in sTBI. Its diagnostic performance and association with axonal injury and outcome support its utility, though longitudinal validation in larger cohorts is required to confirm clinical relevance.