Pathology of the transmissible spongiform encephalopathies with special emphasis on ultrastructure.

The transmissible spongiform encephalopathies are a group of genetic and infectious disorders which are exemplified by scrapie in animals and Creutzfeldt-Jakob disease in humans. The spongiform encephalopathies are characterized by symmetrical vacuolation of neurons and neuropil. Amyloid plaque formation similar to that found in Alzheimer's disease is conspicuous in many, but not all, of these diseases. The sub-cellular pathology features of the spongiform encephalopathies have been studied by conventional transmission electron microscopy, scanning electron microscopy, freeze fracture, negative staining and most recently by application of immunogold labelling methods. Although these studies have revealed many unusual structures, convincing virus-like particles have not been demonstrated. Considerable data, including important transgenic mouse studies, now suggest that a single cellular protein, designated prion protein, is necessary for infection. Ultrastructural immunogold studies have shown that prion protein is released from the surface of neurons and neurites, diffuses through the extracellular space around infected cells where it accumulates and finally becomes aggregated as amyloid fibrils. It is likely that the accumulation of prion protein within the extracellular space is instrumental in causing nerve cell dysfunction and, ultimately, neurological disease.