Here, we examined whether plasma soluble PrP<sup>C</sup> is associated with stroke severity and circulating CD4<sup>+</sup> T cell immune responses in patients with acute ischemic stroke.<h4>Methods</h4>In this single-center prospective cohort study, we consecutively enrolled patients with acute ischemic stroke admitted to the Department of Neurology, The First Hospital of Jilin University (Changchun, China) between June 2023 and October 2024 within 48 h of symptom onset (for wake-up stroke, onset was defined as the last known well). This evidence concerns the gene PRNP and stroke disorder.