PATHOLOGY OF THE TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES WITH SPECIAL EMPHASIS ON ULTRASTRUCTURE

The transmissible spongiform encephalopathies are a group of genetic a nd infectious disorders which are exemplified by scrapie in animals an d 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-cellu lar pathology features of the spongiform encephalopathies have been st udied by conventional transmission electron microscopy, scanning elect ron microscopy, freeze fracture, negative staining and most recently b y 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 tr ansgenic mouse studies, now suggest that a single cellular protein, de signated prion protein, is necessary for infection. Ultrastructural im munogold studies have shown that prion protein is released from the su rface of neurons and neurites, diffuses through the extracellular spac e around infected cells where it accumulates and finally becomes aggre gated as amyloid fibrils. It is likely that the accumulation of prion protein within the extracellular space is instrumental in causing nerv e cell dysfunction and, ultimately, neurological disease.