Blood-Based Analysis of Different Tau Variants in Patients With Multiple Traumatic Injuries

TL;DR

This study shows that blood levels of tau proteins can indicate neurological injury severity in trauma patients, with some tau variants remaining elevated for days after injury.

Contribution

The study demonstrates that blood-based tau biomarkers can reflect both direct and indirect neurological injury in trauma patients.

Findings

Blood levels of tau variants were significantly higher in trauma patients compared to healthy controls.

BD-tau levels remained elevated for up to 10 days post-injury, indicating persistent neurological impact.

Higher tau levels correlated with worse clinical outcomes like lower GCS scores and shock.

Abstract

Are blood-based tau biomarkers clinically useful to monitor neurological injuries in patients with multiple traumatic injuries?

In this cohort study with 69 participants, total, phosphorylated, and brain-derived tau blood levels were significantly elevated in patients with multiple traumatic injuries, with and without head injury. Tau concentrations were associated with injury severity, shock, and clinical outcome.

These findings suggest that further research may inform on the usefulness of blood-based tau biomarkers for monitoring neurological damage and their association with clinical outcomes.

This cohort study evaluates whether there are differences in blood-based phosphorylated and nonphosphorylated tau variant levels in patients with multiple traumatic injuries and healthy controls.

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.

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.

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.

Serum BD-tau, t-tau, p-tau217, and p-tau231 levels.

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).

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.

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