Serum brain-derived tau distinguishes acute neurotrauma diagnoses

Traumatic brain injury (TBI) and spinal cord injury (SCI) are two common forms of neurotrauma that can present with overlapping clinical features, complicating early diagnosis and management particularly in acute and mixed-trauma settings.1 – 3 Accurate and rapid biological differentiation remains an unmet need.4 We hypothesized that brain-derived tau (BD-tau), an ultrasensitive blood-based biomarker preferentially selective for tau protein originating from the brain, would distinguish TBI from SCI. In a multi-cohort assessment of 342 patients admitted to the neuro-intensive care unit (285 with TBI, 57 with SCI), and 22 controls, baseline serum BD-tau concentrations were markedly elevated in TBI compared with SCI, discriminating between the two populations with high accuracy (area under the curve [AUC]=0.91, 95%CI 0.87-0.96). In paired serum-cerebrospinal fluid (CSF) samples, serum BD-tau significantly outperformed CSF BD-tau for injury-type discrimination (AUC=0.95, 95%CI 0.89-0.99 vs. 0.80, 95%CI 0.71-0.89). Baseline serum BD-tau also showed superior discrimination of TBI from SCI compared with established blood biomarkers of neurotrauma, including neurofilament light chain, glial fibrillary acidic protein, and ubiquitin C-terminal hydrolase L1 (AUC=0.82, 95%CI 0.76-0.88; vs. 0.53, 95%CI 0.43-0.63; 0.67, 95%CI 0.58-0.76; 0.71, 95%CI 0.64-0.79; all DeLong p<0.001). Longitudinally, serum BD-tau remained persistently elevated in TBI, but not SCI, for up to 144 hours post-injury, with distinct temporal trajectories between injury types. Together, these findings indicate that serum BD-tau enables rapid and minimally invasive differentiation of TBI from SCI and may support early clinical decision-making, triage, and enrollment into injury-specific therapeutic trials, highlighting the potential of circulating biomarkers to improve precision diagnostics in acute neurotrauma care.