Genetic pleiotropy and the shared pathological features of corticobasal degeneration and progressive supranuclear palsy: a case report and a review of the literature

Though distinct pathological entities, corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) share multiple biochemical and genetic features suggesting overlapping pathophysiology. We report the case of a patient with an 18-year clinical course consistent with behavioral variant frontotemporal dementia. The neuropathological assessment revealed unclassifiable frontotemporal lobar degeneration with tau-immunoreactive inclusions sharing features of both CBD and PSP. Whole-genome sequencing revealed a unique combination of pleiotropic genetic risk variants associated with both PSP and CBD. These findings support the observation that CBD and PSP share genetic co-expression networks that influence neurodegenerative pathogenesis common to 4R tauopathies.

Keywords: Corticobasal degeneration; atypical; frontotemporal dementia; genetics; neuropathology; pleiotropy; progressive supranuclear palsy.