A protease-resistant prion protein isoform is present in urine of animals and humans affected with prion diseases

Prion protein (PrP)(Sc), the only known component of the prion, is present mostly in the brains of animals and humans affected with prion diseases. We now show that a protease-resistant PrP isoform can also be detected in the urine of hamsters, cattle, and humans suffering from transmissible spongif orm encephalopathies. Most important, this PrP isoform (UPrPSc) was also fo und in the urine of hamsters inoculated with prions long before the appeara nce of clinical signs. Interestingly, intracerebrally inoculation of hamste rs with UPrPSc did not cause clinical signs of prion disease even after 270 days, suggesting it differs in its pathogenic properties from brain PrPSc. We propose that the detection of UPrPSc can be used to diagnose humans and animals incubating prion diseases, as well as to increase our understandin g on the metabolism of PrPSc in vivo.