The most widely recognized human prion disease, or transmissible spongiform encephalopathy is variant Creutzfeldt–Jakob disease (vCJD)2. vCJD is related to consumption of beef from cattle infected with bovine spongiform encephalopathy (BSE) colloquially referred to as mad cow disease. Identified in 1996, vCJD was so termed because of its “variant” presentation relative to the fatal neurodegenerative disease first described by Creutzfeldt and Jakob in the 1920s. Unlike the late-onset sporadic-CJD (sCJD, mean onset = 65 years), vCJD had a considerably younger age of onset (mean onset = 26 years) and neuropathology comparable to BSE. New cases of vCJD peaked in 2000 in the United Kingdom and sharply declined with the epidemiological and experimental connection with BSE and introduction of new animal health control measures. Prion disease can be divided into the following 3 major groups: acquired (including vCJD, Kuru, and iatrogenic cases), familial, and sporadic. Although vCJD garners perhaps the greatest attention, it belongs to the group with the smallest incidence proportion (<1%), with sCJD being the most common form of the disease (85% cumulative incidence). What makes prion disease distinctive is the peculiar nature of the infectious agent. The disease is characterized by a change in conformation of an endogenous cellular glycoprotein, the prion protein (PrPC), to a misfolded and aggregate-prone structural conformer termed PrPSc (1). As the disease progresses, PrPSc acts as a template, recruiting newly synthesized PrPC to misfold and thus driving the pathological cascade (Fig. 1). The mature PrPSc aggregates are characterized by their resistance to proteinase K digestion, apple-green birefringence when stained with Congo red, and their ability to enhance the fluorescence emission of the dye thioflavin T. In vitro, conversion of PrPC to PrPSc can be driven by high concentrations of PrP, low pH conditions, chemical …