The addition of oligomeric α-synuclein and PFFs in the absence of genetic alterations results in DA release defects.72,105 Further, many models of Parkinson’s disease-related proteins such as LRRK2, PINK1, GCase and VPS35 report increased α-synuclein expression and aggregation68,137–139 or decreased degradation140 which suggests the pathological mechanisms may occur in many of these models, at least in part, indirectly through α-synuclein. This evidence concerns the gene SNCA and Parkinson disease.