Subtyping Lewy body disorders using proteomics

Lewy body disorders (LBD), characterized by the deposition of misfolded α-synuclein (α-Syn), are clinically heterogeneous. We hypothesized that this heterogeneity might reflect α-Syn molecular diversity, between both patients and different brain regions. Using an ultra-sensitive assay, we evaluated α-Syn seeding from 30 LBD patients with different clinical phenotypes and disease durations. Interestingly, α-Syn from patients with rapid disease progression (<3 years) had a higher nigral seeding capacity than the rest of the patients included. We performed a proteomic-wide profiling of the substantia nigra from 5 high and 5 low seeder patients. The proteomic data suggests a significant disruption in mitochondrial function and lipid metabolism in high seeder cases compared to the low seeders.