This study examined the temporal relationship between α-synuclein (α-syn)-specific T cell reactivity and Parkinson's disease (PD). A longitudinal case study showed elevated α-syn-specific T cell responses before motor PD diagnosis, declining afterward. Two independent cohorts confirmed highest α-syn-specific T cell responses shortly after motor PD diagnosis, decreasing thereafter. These responses correlated with age and lower levodopa equivalent dose. The findings suggest α-syn-reactive T cells are present years before motor PD diagnosis, potentially impacting pathogenesis and early diagnosis.

Cecilia S. Lindestam Arlehamn, Rekha Dhanwani, John Pham, Rebecca Kuan, April Frazier, Juliana Rezende Dutra, Elizabeth Phillips, Simon Mallala, Mario Roederer, Karen S. Marder, Amy V. Amara, David G. Standaert, Jennifer G. Goldman, Irene Litvan, Bjoern Peters, David Sulzer, Alessandro Sette