Alpha-Synuclein-Specific T Cell Reactivity Is Associated With Preclinical And Early Parkinson'S Disease

Abstract A clinical diagnosis of motor Parkinson’s disease (PD) is preceded by a prolonged premotor phase with accumulating neuronal damage. α-Synuclein (α-syn)-specific T cell reactivity is preferentially associated with PD patients. Here we examined the temporal relation between α-syn T cell reactivity and PD. Analysis of PBMCs from a longitudinal case study revealed that elevated α-syn-specific T cell responses were detected prior to the diagnosis of motor PD, and declined after. These results suggest that α-syn-specific proinflammatory T cell reactivity could serve as an early predictor of PD. The relationship between T cell reactivity and early PD was further examined in two independent cohorts, which showed that α-syn-specific T cell responses were highest shortly after diagnosis of motor PD and then decreased. Additional analysis of clinical variables revealed significant association of α-syn-specific T cell responses with age and lower levodopa equivalent dose, and no correlation with motor and cognitive deficits. These results confirm the presence of α-syn-reactive T cells in PD and show that they are most abundant immediately after diagnosis of motor PD. Our single case study suggests that these cells may be present years before the diagnosis of motor PD, suggesting new avenues of investigation into PD pathogenesis, potential early diagnosis, and treatment options.