Unique degeneration signatures in the cerebellar cortex for spinocerebellar ataxias 2, 3, and 7

Spinocerebellar ataxias (SCAs) are a heterogeneous group of neurodegenerative diseases that selectively affect vulnerable neuronal populations in the cerebellum and other subcortical regions. While previous studies have reported subtype differences in the absolute amount of degeneration in specific regions of interest, they failed to account for two important factors. First, they did not control for overall differences in the severity of the degeneration pattern, and second, they did not fully characterize the spatial pattern of degeneration for each SCA subtype. Here, we provide a systematic characterization of the spatial degeneration patterns for three polyQ SCAs (55 patients, either SCA2, SCA3, or SCA7) while controlling for the severity of the degeneration pattern. After this correction, the cerebellar degeneration pattern can successfully classify between the three different SCA subtypes with high cross-validated accuracy. Specifically, degeneration in SCA3 disproportionally affects motor regions of the cerebellar cortex, which explains the relatively severe motor symptoms observed in this subtype. Our results demonstrate that each of the three studied SCA subtypes has a unique cerebellar degeneration signature, hinting at differences in the disease process. Clinically, these differentiable patterns of cerebellar degeneration can be used to reliably discern subtypes, even at relatively early stages of the disease.