Clinical value of plasma brain-derived tau and p-tau217 in acute ischemic stroke

Abstract

Introduction: Diagnosis of acute ischemic stroke (AIS) as based on clinical examination and neuroimaging has limitations in determining subgroup aetiology and subsequent long-term motor and cognitive impairment. Identification of high-risk patients enables personalised prophylaxis and rehabilitation strategies. This study explores the clinical value of plasma brain-derived tau (BD-tau) and phosphorylated-tau217 (p-tau217), primarily associated with neurodegeneration, in identifying patients at risk of sequela after AIS. Methods: We analysed a cohort of 193 patients admitted to the stroke unit at Akershus University Hospital in Oslo, Norway. Each patient received a diagnosis of AIS (n=102), transient ischemic attack (TIA, n=63) or stroke mimic (n=31). Patient characteristics were collected from hospital records. Biomarkers were quantified using Simoa HDX in venous blood sampled obtained the day after admission. Inpatient short-term outcomes, including stroke diameter on magnetic resonance imaging (MRI, n=134) and mini mental state examination (MMSE, n=153), were assessed prior to discharge. Non-parametric statistics, including Kruskal-Wallis and Kendall´s tau-b correlation tests were applied. Backwards stepwise linear regression analysis was used to determine the association between stroke diameter or MMSE and the biomarkers. A full model was fitted with explanatory variables as listen in table 1. Results: BD-tau was significantly increased in AIS patients as compared to mimics (p=.004), whereas p- tau217 did not differentiate between the diagnostic groups. MRIs were available for 66 (64.7%) of AIS patients, of whom n=36 were diagnosed with cortical and n=30 with subcortical stroke. Cortical stroke diameter showed a strong correlation with BD-tau (fig. 1, <.001) and p-tau217 (=.003). In regression analysis, only BD-tau was found to be significantly associated with stroke diameter (table 1). Subcortical strokes were mot associated with any of the biomarkers. Furthermore, MMSE score correlated with BD-tau (fig. 2, <.001) and p-tau217 (<.001). In regression analysis, age was the strongest predictor of MMSE score, followed by p-tau217. Discussion: Our findings suggest that blood-based BD-tau and p-tau217 have clinical potential in determining AIS subgroup aetiology and provide insights into cognitive impairment in AIS patients. These findings may have implications for rehabilitation and secondary prophylaxis after stroke.