This research investigates alpha-synuclein (aSyn) strains in Lewy body diseases (LBDs), specifically Parkinson's disease (PD) and Dementia with Lewy bodies (DLB). The study utilized monoclonal antibodies to detect distinct aSyn species, termed strain A and strain B, in various human biological samples. Significantly, higher levels of both strain A and B aSyn were found in the plasma of individuals with PD compared to those with DLB. The authors also found that lower levels of plasma aSyn strain A correlated with a faster rate of cognitive decline in PD patients. Importantly, these plasma aSyn species demonstrated pathogenic potential, capable of inducing aSyn fibrillization in vitro and aggregate formation in cell models, suggesting their role in disease progression and as potential biomarkers.