Subsequently, data from native velocity gradient fractionation and conformation-dependent immunoassays defined a progressive fall in levels of PrPC and the PrP-like, GPI-anchored shadoo protein (Sho) at pre-symptomatic stages of prion diseases; these data offer a simple explanation for the plateau in titer levels during the disease incubation period [5, 6, 43]. This evidence concerns the gene PRNP and prion disease.