Assessing Prion Infectivity of Human Urine in Sporadic Creutzfeldt-Jakob Disease

Abstract

Prion diseases are neurodegenerative conditions associated with a misfolded and infectious protein, scrapie prion protein (PrPSc). PrPSc propagate prion diseases within and between species and thus pose risks to public health. Prion infectivity or PrPSc presence has been demonstrated in urine of experimentally infected animals, but there are no recent studies of urine from patients with Creutzfeldt-Jakob disease (CJD). We performed bioassays in transgenic mice expressing human PrP to assess prion infectivity in urine from patients affected by a common subtype of sporadic CJD, sCJDMM1. We tested raw urine and 100-fold concentrated and dialyzed urine and assessed the sensitivity of the bioassay along with the effect of concentration and dialysis on prion infectivity. Intracerebral inoculation of transgenic mice with urine from 3 sCJDMM1 patients failed to demonstrate prion disease transmission, indicating that prion infectivity in urine from sCJDMM1 patients is either not present or is <0.38 infectious units/mL.

Keywords

• prions
• prions and related diseases
• Creutzfeld-Jakob disease
• neurodegenerative diseases
• transmissible spongiform encephalopathy
• infectivity