Transmissible Spongiform Encephalopathy Neurobiology and Ultrastructure Suggests Extracellular PrPSc Conversion Consistent with Classical Amyloidosis.

The infectious cause of the transmissible spongiform encephalopathies (TSEs), or prion diseases, is not yet clearly defined. Although minorities of researchers cling tenaciously to the virus hypothesis, the prion or protein-only hypothesis is now widely accepted by most scientists working in this field (1). When originally formulated, the protein-only hypothesis proposed that the TSE agent was an abnormal infectious form of a host-coded protein (protease-resistant protein, or prion protein) that could convert homologous normal forms of the protein into replicates of itself (2).