Abstract
IMPORTANCE: With blood-based phosphorylated tau biomarkers soon to be used for diagnosis of Alzheimer disease, analyzing tau levels in other conditions could enhance biomarker interpretability. Moreover, mechanisms of tau release into circulation remain unclear. OBJECTIVE: To evaluate concentrations of phosphorylated and nonphosphorylated tau variants in the blood of patients with multiple traumatic injuries on days 0, 1, 5, and 10 and investigate biological processes driving tau release. DESIGN, SETTING, AND PARTICIPANTS: This multiple-trauma cohort (injury severity score, ≥18) included 45 severely injured patients with (n = 27) and without (n = 18) moderate-to-severe traumatic brain injury on emergency computed tomographic imaging. Controls consisted of 24 healthy volunteers. Participants were recruited from December 1, 2013, to October 31, 2022. Blood samples were analyzed for brain-derived tau (BD-tau), total tau (t-tau), and phosphorylated tau 217 (p-tau217) and 231 (p-tau231) levels. Associations among tau concentrations, clinical data, and outcome (eg, Glasgow Coma Scale [GCS] score) were assessed. Data were analyzed from March 1, 2023, to September 30, 2024. EXPOSURES: Serum BD-tau, t-tau, p-tau217, and p-tau231 levels. RESULTS: A total of 214 serum samples were analyzed. Median age of the 45 patients was 48 (IQR, 33-60) years (35 [77.8%] male); median age of the 24 controls, 43 (IQR, 28-50) years (16 [66.7%] male). Median serum levels of tau variants were increased in patients with multiple traumatic injuries at day 0 compared with controls (t-tau: 43 [IQR, 21-95] vs 3 [IQR, 3-5] pg/mL; BD-tau: 78 [IQR, 30-343] vs 2 [IQR, 2-3] pg/mL; p-tau231: 61 [IQR, 21-79] vs 2 [IQR, 1-3] pg/mL; all, P < .001). Only median BD-tau levels remained elevated until day 10 (day 1, 25 [IQR, 14-69] pg/mL; day 5, 9 [IQR, 4-15] pg/mL; day 10, 8 [IQR, 4-18] pg/mL). Median tau levels at admission were higher in patients with lower GCS scores (BD-tau: 107 [ IQR, 59-838] vs 33 [IQR, 24-78] pg/mL [P = .01]; p-tau231: 76 [IQR, 36-114] vs 28 [IQR, 9-63] pg/mL [P = .02]). Elevated median tau levels were also observed in patients with hemorrhagic shock vs those without shock (eg, BD-tau on day 0: 113 [IQR, 78-378] vs 31 [IQR, 24-61] pg/mL; P = .002) and in nonsurvivors vs survivors with uncomplicated courses (eg, BD-tau on day 1: 92 [IQR, 22-527] vs 16 [IQR, 7-23] pg/mL; P = .009). CONCLUSIONS AND RELEVANCE: In this exploratory study among a cohort of patients with multiple traumatic injuries, levels of tau variants reflected both direct and indirect neurological injury, with BD-tau showing the most persistent elevation in the acute phase.