Deposition of α-synuclein aggregates occurs widely in the central and peripheral nervous systems in Parkinson’s disease (PD). Although recent evidence has suggested that cell-to-cell transmission of α-synuclein aggregates drives the progression of PD, the mechanism by which α-synuclein aggregates spread remains undefined. Here, we show that α-synuclein aggregates are perpetually transmitted through a continuous cycle involving uptake of external aggregates, co-aggregation with endogenous α-synuclein, and exocytosis of the co-aggregates. Moreover, we found that glucocerebrosidase depletion, which has previously been strongly associated with PD and increased cognitive impairment, promoted propagation of α-synuclein aggregates. These studies define how α-synuclein aggregates spread among neuronal cells and explain how glucocerebrosidase mutations increase the risk of developing PD and other synucleinopathies.