Parkinson’s disease is the second most common neurodegenerative disorder that results in motor dysfunction and eventually cognitive impairment. -Synuclein protein has been known to be the most culprit protein but the clear pathological mechanism remains to be elucidated. As an effort to clarify the pathogenesis mechanism by -synuclein, various Parkinson’s disease mouse models with -synuclein overexpression have been developed. However, the systemic analysis of protein abundance change by the overexpressed -synuclein in whole proteome level still has been lacking. To address this issue, we established two different types of Parkinson’s disease model mice by injecting preformed -synuclein fibrils or inducing the expression of A53T mutant -synuclein to discover overlapping pathway, which is altered in the two different types of Parkinson’s disease mouse models. For more accurate quantification of mouse brain proteome, stable isotope labeling with amino acid in mammal-based quantification was implemented. As a result, we have successfully identified a total of 8,355 proteins from both of the mouse models; ~6,800 and ~7,200 proteins from preformed -synuclein fibrils injected model and A53T mutant -synuclein over-expressing model, respectively. From the pathway analysis of the differentially expressed proteins in common, complement and coagulation cascade pathway was recognized as the most enriched one. This is the first study that sheds light on the significance of the complement and coagulation pathway in the pathogenesis of PD through proteome analyses with two different types of Parkinson’s disease mouse models.