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
• progressive supranuclear palsy
• genetics
• pleiotropy
• neuropathology
• frontotemporal dementia
• atypical

Acknowledgments

We thank the research participant and his family for their generous contribution to science.

Supplementary material

Supplemental data for this article can be accessed here.

Disclosure statement

Adam L. Boxer has received research support from NIH, the Tau Research Consortium, the Association for Frontotemporal Degeneration, Bluefield Project to Cure Frontotemporal Dementia, Corticobasal Degeneration Solutions, the Alzheimer’s Drug Discovery Foundation, and the Alzheimer’s Association. He has served as a consultant for Aeton, Abbvie, Alector, Amgen, Arkuda, Arvinas, Asceneuron, Ionis, Lundbeck, Novartis, Passage BIO, Samumed, Third Rock, Toyama, and UCB, and received research support from Avid, Biogen, BMS, C2N, Cortice, Eli Lilly, Forum, Genentech, Janssen, Novartis, Pfizer, Roche, and TauRx. Salvatore Spina has received compensation for consultation work with Precision Xtract and Acsel Health. Other authors have no conflicts to disclose.

Additional information

Funding

This work was funded by the National Institute on Aging P01AG019724, P30AG062422, K08AG052648, R01AG048234, R01AG038791, R01AG032289, R01AG048234, the Larry L. Hillblom Foundation, and the Rainwater Charitable Foundation.