Effects of α-synuclein immunization in a mouse model of Parkinson's disease

Abnormal folding of alpha-synucleln (alpha-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)alpha-syn might have therapeutic effects in LBD. For this purpose, h alpha-syn transgenic (tg) mice were vaccinated with h alpha-syn. In mice that produced high relative affinity antibodies, there was decreased accumulation of aggregated h alpha-syn in neuronal cell bodies and synapses that was associated with reduced neurodegeneration. Furthermore, antibodies produced by immunized mice recognized abnormal h alpha-syn associated with the neuronal membrane and promoted the degradation of h alpha-syn aggregates, probably via lysosomal pathways. Similar effects were observed with an exogenously applied FITC-tagged h alpha-syn antibody. These results suggest that vaccination is effective in reducing neuronal accumulation of h alpha-syn aggregates and that further development of this approach might have a potential role in the treatment of LBD.