Neuropathology of human prion diseases (spongiform encephalopathies)

The human prion diseases (spongiform encephalopathies) comprise Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome (GSS), and kuru. Their clinical characteristics are progressive neurological illness with dementia and ataxia as the most prominent signs. The typical neuropathological changes are limited to the central nervous system; they consist of spongiform degeneration, amyloid plaques, astrocytic gliosis, and nerve cell loss. The aetiology of human spongiform encephalopathies remained unclear for many years, until in the 1960s they were finally recognized as transmissible diseases similar to scrapie in sheep. The infectious agent, termed prion to distinguish it from viruses, consists of protein apparently devoid of functional nucleic acid. The finding that mutations of the prion protein gene are associated with heritable human prion disease has led to wide acceptance of the prion hypothesis. Different mutations have been found in prion disease with distinct clinical and pathological features in a great number of families. Clinical and neuropathological changes not typical of any known variant of human prion disease have been shown to be associated with certain mutations of the PrP gene. Further findings on the molecular biology and biochemistry of the prion protein will probably lead to a new classification of prion diseases.