Pathology is the study of the structural and functional changes produced by diseases or ? more specifically ? the lesions they cause. To achieve this pathologists employ various approaches. These include description of lesions that are visible to the naked eye which are the subject of anatomic pathology and changes at the cellular level that are visible under the microscope, the subject of histopathology. Changes at the molecular level which are identified by probes that target specific molecules ? mainly proteins that are detected using immunohistochemistry (IHC). As transmissible spongiform encephalopathies (TSEs) do not cause visible lesions anatomic pathology is not applicable to their study. For decades the application of histopathology to detect vacuoles or plaques was the only means of confirming TSE disease. The subsequent discovery of the cellular prion protein (PrP~(C)) and its pathogenic isoform, PrP~(Sc), which is a ubiquitous marker of TSEs, led to the production of anti-PrP antibodies, and enabled the development of PrP~(Sc) detection techniques such as immunohistochemistry, Histoblot and PET-blot that have evolved in parallel with similar biochemical methods such as Western blot and ELISA. These methods offer greater sensitivity than histopathology in TSE diagnosis and crucially they can be applied to analyze various phenotypic aspects of single TSE sources increasing the amount of data and offering higher discriminatory power. The above principles are applied to diagnose and define TSE phenotypes which form the basis of strain characterisation.
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