Publication Date
1-1-2025
Journal
Frontiers in Neurology
DOI
10.3389/fneur.2025.1632679
PMID
40808925
PMCID
PMC12344560
PubMedCentral® Posted Date
7-30-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Introduction: Tauopathies, 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).
Methods: CSF 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.
Results: CSF 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).
Discussion: These 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.
Keywords
traumatic brain injury, CSF biomarkers, pTau-217, neurotrauma prognostics, diagnostic biomarkers
Published Open-Access
yes
Recommended Citation
Yadikar, Hamad; Kobeissy, Firas H; Robertson, Claudia; et al., "Early Cerebrospinal Fluid Elevations of pTau-217 in Severe Traumatic Brain Injury Subjects" (2025). Faculty and Staff Publications. 5288.
https://digitalcommons.library.tmc.edu/baylor_docs/5288