Serum tau and p-tau as diagnostic and prognostic tools for pediatric traumatic brain injury

Introduction: The aim of this study was to assess the utilization of tau and tau phosphorylated at the threonine 181 (p-tau181) residue as diagnostic and prognostic neuronal blood-based biomarkers in the setting of mild and moderate pediatric traumatic brain injury (pTBI) according to the Glasgow Coma Scale (GCS) and Glasgow Outcome Scale Extended Pediatrics (GOS-E Peds). Methods: In this prospective observational study, we included 29 patients aged 0-18 years who sustained a mild/moderate pTBI (GCS 9-15) and 19 healthy controls (HC). Serum samples of tau and p-tau were collected and analyzed at the time of enrollment (0 hours), with follow-up measurements at 24 and 48 hours post-injury. Receiver operating characteristics (ROC) and statistical comparisons were performed to analyze plasma biomarker concentrations and GCS severity, as well as binary GOS-E Peds outcome (5-8 = unfavorable, 1-4 = favorable), which was evaluated at 2-6 weeks, 6-9 months, and 12 months post-injury. Data were analyzed utilizing Prism 9 software. Results: Tau and p-tau levels were significantly elevated in patients who sustained mild/moderate pTBI compared to HC at 0h post-injury (p-value 0.017 and 0.001, respectively); with an AUC of 0.84 for tau and a 95% confidence interval (CI) between 0.71 and 0.97, and an AUC of 0.87 for p-tau with a 95% CI between 0.75 and 0.99. Furthermore, p-tau levels were also elevated at 48h post-injury versus HC (p-value 0.031) with an AUC of 0.93 and a 95% CI between 0.83 and 1.00. Our preliminary data suggest that p-tau measured at 0h could possibly predict unfavorable outcomes at 2-6 weeks and 6-9 months post-injury (p-value 0.014 and 0.021, accordingly) with an AUC of 0.90 for p-tau at 2-6 weeks and 0.80 at 6-9 months. In addition, when tau was measured at 0h, it correlated with outcome prediction at 12 months (p-value 0.004) with an AUC of 1.00. Conclusions: Serum tau and p-tau levels were elevated in mild/moderate pTBI subjects at 0h post-injury compared to HC. Thus, examining the relationship between elevations of these proteins following brain trauma with the GOS-E Peds at 2-6 weeks, 6-9 months, and 12 months post-injury could potentially assist with diagnosing pTBI and may help predict neurological outcomes.