Scientific Journal

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

Abstract
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.