Neuronal accumulation of alpha- and beta-synucleins in the brain of a GM2 gangliosidosis mouse model.

Sandhoff disease (SD) is a heritable lysosomal storage disease resulting from impaired degradation of GM2 ganglioside. The hall-mark pathology of the SD model mouse brain is GM2 ganglioside accumulation in neurons. In the present study, we immunohistochemically investigated the neuronal pathology in SD mouse brains, and demonstrated neuronal accumulation of α- and β-synucleins in addition to GM2 ganglioside. Synuclein-positive neurons were extensively observed throughout SD mouse brains, although the distribution of β-synuclein was less extensive than that of α-synuclein. Synuclein-positive neurons were negative to ubiquitin and PHF-tau. These findings suggest that neuronal synucleins may accumulate secondarily to GM2 ganglioside in SD mouse brains, and that neuronal accumulation of synucleins may be more critical than that of GM2 ganglioside for SD mice.