α-Synuclein-specific T cell reactivity is associated with preclinical and early Parkinson's disease

A diagnosis of motor Parkinson's disease (PD) is preceded by a prolonged premotor phase with accumulating neuronal damage. Here we examined the temporal relation between alpha -synuclein (alpha -syn) T cell reactivity and PD. A longitudinal case study revealed that elevated alpha -syn-specific T cell responses were detected prior to the diagnosis of motor PD, and declined after. The relationship between T cell reactivity and early PD in two independent cohorts showed that alpha -syn-specific T cell responses were highest shortly after diagnosis of motor PD and then decreased. Additional analysis revealed significant association of alpha -syn-specific T cell responses with age and lower levodopa equivalent dose. These results confirm the presence of alpha -syn-reactive T cells in PD and show that they are most abundant immediately after diagnosis of motor PD. These cells may be present years before the diagnosis of motor PD, suggesting avenues of investigation into PD pathogenesis and potential early diagnosis. alpha -Synuclein-specific T cell reactivity is preferentially associated with Parkinson's disease (PD) patients, but the temporal relation with diagnosis was previously unknown. This study reveals that alpha -syn-reactive T cells are highest before and shortly after diagnosis of motor PD, and then decrease.