Prion infections, or Transmissible Spongiform Encephalopathies (TSEs), result in progressive, fatal neurodegeneration. No effective therapies are available, and medical interventions, possibly including blood transfusions, have resulted in human-to-human transmission of prions. However, no biomarkers are available for preclinical diagnosis of prion infection in body fluids. All approved methods of diagnosis rely exclusively on detection of pathological prion protein (PrPSc), which may not be present in all TSEs. We have recently identified two secreted proteins, levels of which are profoundly increased in preclinical prion infections. We have been able to demonstrate that levels of one of these surrogate marker proteins investigated so far are elevated in fluids of sporadic CJD patients, particularly in urine. In this applied project we will field-test the validity of our recently identified markers for efficacy of predictive screening potential for preclinical identification of prion diseases of animals such as BSE in cattle and scrapie in sheep, utilising easily accessible bodily fluids such as urine and sera.