Ovine serum biomarkers of early and late phase scrapie

In this study we used the SELDI-TOF MS technology to analyze a large number of serum samples from control sheep and animals with early phase or late phase scrapie. A few potential low molecular weight biomarkers were selected by statistical methods and, after a training analysis, a protein signature pattern, which discriminates between early phase scrapie samples and control sera was identified.The combination of early phase biomarkers showed a sensitivity of 87% and specificity of 90% for all studied sheep in the early stage of the disease. One of these potential biomarkers was identified and validated in a SELDI-TOF MS kinetic study of sera from Syrian hamsters infected by scrapie, by western blot analysis and ELISA quantitation.Differential protein expression profiling allows establishing a TSE diagnostic in scrapie sheep, in the early phase of the disease. Some proteic differences observed in scrapie sheep exist in infected hamsters. Further studies are being performed to identify all the discriminant biomarkers of interest and to test our potential markers in a new cohort of animals.Scrapie is a well-known prion-associated sheep encephalopathy that was identified in the XVIII century. Scrapie is a fatal neurodegenerative disease and related forms affect also humans (i.e., Creutzfeldt-Jakob disease) and cattle (i.e., bovine spongiform encephalopathy). It is characterized by accumulation in the central nervous system of a pathological agent, the prion protein (PrPSc) [1], which differs from the endogenous normal form (PrPc) in conformational changes, partial resistance to proteolytic degradation and insolubility in the presence of detergents [2,3]. Scrapie is a good model to study transmissible spongiform encephalopathies (TSEs) since the disease is related to genetic factors. The natural occurrence of scrapie is associated with the PRNP genotype at positions 136, 154, 171 [4-6]. Specifically, infected animals present the homozygous PrPVRQ/PrPVRQ genotype, wherea