The invention relates to diagnostic methods and kits for detecting transmissible spongiform encephalopathies (TSEs) such as BSE, scrapie, chronic wasting disease and related diseases in animals and humans. The invention provides a method for determining whether an aberrant prion protein is present or absent in a mammalian sample comprising the steps of preparing in an extraction buffer that comprises a surfactant and a detergent a homogenate from said sample, incubating said homogenate in diluted extraction buffer with a protease, incubating with a chaotropic agent and at least one washing buffer and detecting said aberrant prion protein.