Concentration of Disease-Associated Prion Protein with Silicon Dioxide

Reagents that can precipitate the disease-associated prion protein (PrPSc) are vital for the development of high sensitivity tests to detect low levels of this disease marker in biological material. Here, a range of minerals are shown to precipitate both ovine cellular prion protein (PrPC) and ovine scrapie PrPSc. The precipitation of prion protein with silicon dioxide is unaffected by PrPSc strain or host species and the method can be used to precipitate bovine BSE. This method can reliably concentrate protease-resistant ovine PrPSc (PrPres) derived from 1.69 mu g of brain protein from a clinically infected animal diluted into either 50 ml of buffer or 15 ml of plasma. The introduction of a SiO2 precipitation step into the immunological detection of PrPres increased detection sensitivity by over 1,500-fold. Minerals such as SiO2 are readily available, low cost reagents with generic application to the concentration of diseases-associated prion proteins.