Plasma Profile of Brain-Derived Tau After Ischemic Stroke.

Abstract

Background and aim: Brain-derived tau (BD-tau) is a predominantly CNS-derived form of tau protein detectable in blood that reflects brain injury and has emerged as a potential biomarker in ischemic stroke for assessing neuronal damage, monitoring infarct progression, and predicting functional outcome. However, its temporal profile and the optimal timing for correlation with infarct volume remain unclear.

Methods: This prospective cohort study included patients with ischemic stroke, with venous blood samples collected daily during the first week and at 3 months after symptom onset. Infarct volume was assessed by MRI at 48-72 h. Plasma BD-tau concentrations were measured using a Simoa assay. Linear mixed-effects models were used to analyze changes in biomarker levels. The optimal time point for correlation between BD-tau and infarct volume was identified using a 24-h moving-window Pearson correlation analysis.

Results: Fifty-four patients (median age 78 years, 50% female) contributed 285 plasma samples. Plasma levels of BD-tau followed a parabolic trajectory reaching a peak approximately 5 days after symptom onset. After 90 days, the concentration of BD-tau was lower than in the last measurement of the first week. The strongest correlation between BD-tau and infarct volume occurred at 105 h (4.4 days) (r = 0.89, 95% CI: 0.78-0.95) after symptom onset.

Conclusions: Plasma BD-tau exhibits a distinct temporal profile after ischemic stroke, with peak levels and maximal correlation with infarct volume occurring around Day 4-5. These findings have important implications for interpreting BD-tau levels and optimizing sampling strategies in clinical studies.

Trial registration: Clinicaltrials.gov NCT03812666.