Saturday, May 10, 2025
5/10/2025
Identifying the genetic basis of variably protease-sensitive prionopathy - PROJECT SUMMARY First characterized one decade ago, VPSPr is a rare neurodegenerative disease that presents clinically as Lewy body dementia or frontotemporal lobar degeneration but has been neuropathologically linked to deposits of infectious but protease-sensitive prion protein (PrP) aggregates. VPSPr cases lack mutations in the prion protein gene (PRNP) but 42% of cases have a positive family history, consistent with a genetic disease of moderate penetrance. We will apply whole exome sequencing and deep targeted sequencing to query the genetic basis of VPSPr. Identification of a genetic cause of VPSPr will aid in the differential diagnosis of prion disease and Alzheimer’s-related dementias, validate new genomic technologies for understanding neurodegeneration, and identify new cellular pathways that lead to neurodegenerative disease.
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