Canello et al. show that while an antibody (pAB RVC) specific to helix 3 buried methionines (M205/206/213) was able to readily detect huPrP in brain homogenates of healthy individuals and patients of sporadic prion disease, PrP in brain homogenates of individuals heterozygous for E200K was poorly detected [74]. Here, PRNP is linked to prion disease.