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Background: Diffuse axonal injury (DAI) is difficult to identify in the early phase of traumatic brain injury (TBI) using common diagnostic methods. Tau protein is localized specifically in nerve axons. We hypothesized that serum level of tau can be a useful biomarker to diagnose DAI in the early phase of TBI. Methods & results: We measured serum tau levels in 40 TBI patients who were suspected of DAI within 6 hours after TBI to evaluate the accuracy of the tau level as a diagnostic marker for DAI. Diagnosis of DAI was confirmed according to magnetic resonance imaging (MRI) findings. The serum tau level in the DAI group (n = 13) was significantly higher than that in the non-DAI group (n = 27) (DAI vs. non-DAI, 25.3 [0 to 99.1] pg/mL vs. 0 [0 to 44.4] pg/mL, P = 0.03)). A receiver-operating characteristic curve to evaluate the diagnostic ability of serum tau level within 6 hours for DAI showed an area under the curve of 0.690 with 74.1% for sensitivity and 69.2% for specificity. Serum tau level was not significantly higher in unfavorable outcome group (Glasgow Outcome scale [GOS] score = 1–3 at hospital discharge) compared with favorable outcome group (GOS score = 4–5) (P = 0.19). Conclusions: Tau protein may be a useful biomarker for diagnosis of DAI in the early phase of TBI. [ABSTRACT FROM AUTHOR]