α-Synuclein (α-syn) may promote Parkinson's disease–like pathology by cell-to-cell transmission in mice, according to a new report in Science (338, 949–953, 2012).

Credit: Equinox Graphics / Science Source

Previous studies have suggested that in Alzheimer's disease, pathology can spread between interconnected brain regions by cell-to-cell transmission of the pathogenic peptides amyloid-β and tau. In Parkinson's disease, Lewy body–like inclusions containing α-syn have previously been detected in embryonic nigral transplants from patients with Parkinson's disease, suggesting that Parkinson's pathology may be able to spread from host cells to the donor grafts.

Virginia M.-Y. Lee and her colleagues now report that in wild-type mice, a single injection of preformed fibrillar α-syn into the striatum is sufficient to induce intraneuronal α-syn accumulation and Lewy body pathology. Over time, pathology spread in a stereotypic fashion between connected brain regions, potentially seeding aggregation of endogenous α-syn. This eventually led to the loss of dopaminergic neurons, a reduction in dopamine within affected regions, and a concomitant impairment in motor function compared with untreated mice. These findings suggest that the aggregation of α-syn is sufficient to recapitulate the pathological hallmarks of Parkinson's disease and that it may promote disease by cell-to-cell transmission.