Human Prion Diseases

Abstract This chapter presents the current understanding of prion disorders and the pathogenesis of propagation of misfolded prion protein. The human prion diseases include sporadic, genetic, and acquired disorders. Accurate diagnosis of human prion diseases therefore requires a combined clinical, neuropathologic, genetic, and biochemical approaches. The most current recommendations include routine histologic evaluation with immunohistochemistry for prion protein. Unfixed frozen brain tissue is critical for analysis of the protease-resistant prion protein isoform and for DNA extraction to allow sequencing of the prion protein gene. The assessment of spongiform change, gliosis, neuronal loss, and the patterns of accumulation of the disease-associated prion protein in the brain can determine the major categories of human prion disease. Additional clinical, genetic, and biochemical data then allow accurate subclassification into disease subtypes, particularly in sporadic Creutzfeldt–Jakob disease (CJD). Variant CJD caused by exposure to bovine spongiform prions is reviewed, along with the expanding spectrum of human prion diseases currently known.