Chapter 23 – Prion Diseases

Prion diseases or transmissible spongiform encephalopathies are neurodegenerative (non-inflammatory) diseases characterized by deposition in the CNS and some other organs of misfolded isoform of prion protein (PrPd). In humans, they include kuru, Creutzfeldt–Jakob disease (CJD), Gerstmann–Straussler–Scheinker disease, fatal familial insomnia, and variably protease-sensitive prionopathy. In animals, they include scrapie in sheep, goats, and mouflons; bovine spongiform encephalopathy; chronic wasting disease in cervids; and transmissible mink encephalopathy. The conversion of a normal cellular isoform of PrP into its misfolded pathological isoform PrPd underlies their pathogenesis. The concern is that other neurodegenerations, e.g. Alzheimer disease, Parkinson disease, tauopathies, and amyotrophic lateral sclerosis, in which misfolded proteins play a major role, may also exhibit prion-like properties. This chapter reviews the etiology, pathogenesis, molecular subtypes, and neuropathology of prion diseases, as well as the mutations causing hereditary forms of prion diseases. Sections on variant CJD and prionoids are also included.