Prions and transmissible spongiform encephalopathies

The transmissible spongiform encephalopathies (TSEs) are a unique suite of progressive neurodegenerative diseases that show both infectious and hereditable transmission characteristics. TSEs have been observed in various mammals including humans, and as yet no treatment is available. The pathogenic agent replicates in a number of tissues including spleen and liver, before appearing in high concentrations in the brain and cen- tral nervous system (CNS) towards the terminal stages of the disease. Ultimately, severe degeneration of the brain and spinal cord lead to clinical signs and the condition is then invariably fatal within several months. Pathologically the disease is characterized by the appearance of abnormal protein deposits (amyloids) in the kidney, spleen, liver, and brain. Amyloids arise from the accumulation of various proteins, which take the form of plaques or fibrils. Amyloidosis is also a characteristic feature of Alzheimer’s disease, and although this condition is not transmissible, a prion-based pathology has not been totally eliminated. The protein deposits are insoluble and hence cytotoxic, leading to cell death and a sponge-like appearance of the brain, which gave the spongiform encephalopathies their name; microscopic holes can be visualized in thin sections of brain tissue taken at post mortem. There is no conventional immune response to the agent, although the immune system plays an important part in the development of the disease before the agent gets into the CNS. Diagnosis of TSEs is difficult and  for some time could only be made by immunohistochemical staining of the  prion protein in tissue taken at post mortem, although there have been some examples of diagnosis based on detection of the prion protein in cerebrospinal fluid (CSF) or tonsillar tissue.