Abstract: This application includes description of antibodies for specifically detecting prions of human origin and methods for detecting pathogenic prions. In some embodiments, the antibodies bind to an epitope characteristic of a human prion protein which is not found in the prion proteins of other species. In some embodiments, the antibodies are not cross-reactive with cow, Syrian Gold hamster, mouse, or rat prions. The application also includes a conformation-dependent immunoassay method for detecting pathogenic prions in a sample containing a prion (PrP) protein. The PrP protein may be present in a first conformation and a second conformation, such as PrPc and PrPSc in which the two conformations have different binding affinity for the antibody used to detect them.