Our study demonstrates that suppression of endogenous Snca gene expression by pre-treatment with Snca ASOs at the aSyn PFFs inoculation (seeding) site prevented the progression of various pathological changes, including the appearance of pSyn pathology in the whole brain and abnormal pSyn insolubilization in our mouse aSyn pathological transmission models of PD and DLB. Here, SNCA is linked to Parkinson disease.