Elevated plasma levels of alpha-synuclein are dispensable for Parkinson's disease pathology.

Although α-synuclein levels are elevated in the blood plasma of Parkinson's disease (PD) patients, it remains unclear whether blood-derived α-synuclein directly contributes to PD. To investigate this, we developed a novel mouse model in which human α-synuclein levels are increased in the blood. Despite a significant increase in α-synuclein in the blood, no noticeable behavioral abnormalities were observed in aged mice. Additionally, we did not observe plasma α-synuclein aggregation in the blood or entry of human α-synuclein into the brain. These results suggest that elevated blood levels of α-synuclein may not be sufficient to induce PD progression.