Effects of α-Synuclein Immunization in a Mouse Model of Parkinson’s Disease

Abnormal folding of -synuclein ( -syn) is thought to lead to neurodegeneration and the characteristic symptoms of Lewy body disease (LBD). Since previous studies suggest that immunization might be a potential therapy for Alzheimer’s disease, we hypothesized that immunization with human (h) -syn might have therapeutic effects in LBD. For this purpose, h syn transgenic (tg) mice were vaccinated with h -syn. In mice that produced high relative affinity antibodies, there was decreased accumulation of aggregated h syn in neuronal cell bodies and synapses that was associated with reduced neurodegeneration. Furthermore, antibodies produced by immunized mice recognized abnormal h -syn associated with the neuronal membrane and promoted the degradation of h -syn aggregates, probably via lysosomal pathways. Similar effects were observed with an exogenously applied FITC-tagged h -syn antibody. These results suggest that vaccination is effective in reducing neuronal accumulation of h -syn aggregates and that further development of this approach might have a potential role in the treatment of LBD.