α-Synuclein transfer between neurons and astrocytes indicates that astrocytes play a role in degradation rather than in spreading

Recent evidence suggests that disease progression in Parkinson's disease (PD) could occur by the spreading of alpha-synuclein (alpha-syn) aggregates between neurons. Here we studied the role of astrocytes in the intercellular transfer and fate of alpha-syn fibrils, using in vitro and ex vivo models. alpha-Syn fibrils can be transferred to neighboring cells; however, the transfer efficiency changes depending on the cell types. We found that alpha-syn is efficiently transferred from astrocytes to astrocytes and from neurons to astrocytes, but less efficiently from astrocytes to neurons. Interestingly, alpha-syn puncta are mainly found inside the lysosomal compartments of the recipient cells. However, differently from neurons, astrocytes are able to efficiently degrade fibrillar alpha-syn, suggesting an active role for these cells in clearing alpha-syn deposits. Astrocytes co-cultured with organotypic brain slices are able to take up alpha-syn fibrils from the slices. Altogether our data support a role for astrocytes in trapping and clearing alpha-syn pathological deposits in PD.