Variably Protease-sensitive Prionopathy in an Apparent Cognitively Normal 93-Year-Old

Variably protease-sensitive prionopathy (VPSPr) is a recently described novel prion disease biochemically characterized by abnormal prion protein (PrP) which has various degrees of sensitivity to proteases and generates a distinct profile on Western blots 1. VPSPr is the second most common sporadic prion protein disease after CJD 2. All reported cases to date have exhibited cognitive, behavioral, and psychiatric deficits with an age at onset range of 48-81 years and disease duration range of 7-72 months 1-4. Initial clinical diagnoses included normal pressure hydrocephalus (NPH), dementia with Lewy bodies (DLB), or frontotemporal dementia (FTD) 1,5, but Creutzfeldt-Jakob disease (CJD) often was considered clinically after rapid decline became apparent 1. All VPSPr cases evaluated have lacked mutations in the prion protein gene (PRNP) 1,2,5. Initial reports indicated all cases were homozygous for valine at codon 129 (VV) in PRNP 1. However, more recent reports have found VPSPr in all three codon 129 genotypes 2,5-7. Here we report a case of VPSPr in which there were no known clinical manifestations of prion disease during life and yet pathognomonic findings were revealed at autopsy.