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Prions are proteins that adopt alternative conformations, which become self-propagating. Some prions cause degeneration of the central nervous system (CNS). Once relegated to causing a group of rare CNS disorders, such as Creutzfeldt-Jakob disease (CJD), increasing evidence argues that prions cause more common neurodegenerative diseases (NDs) including Alzheimer’s disease (AD) and Parkinson’s disease (PD). While CJD is caused by the accumulation of PrPSc prions, recent investigations demonstrate unequivocally that α-synuclein prions cause multiple system atrophy (MSA) (Chap. 440). Infectious MSA prions have been recovered from human brain samples stored in formalin for up to 20 years. Similar resistance to formalin was demonstrated for brain samples from sheep with scrapie. Increasingly, studies show that Aβ and tau prions together cause AD, α-synuclein prions cause both PD and MSA, and tau prions alone cause frontotemporal lobar degeneration (FTLD). In this chapter, we confine our discussion to CJD, which typically presents with a rapidly progressive dementia as well as motor and behavioral abnormalities. The illness is relentlessly progressive and generally causes death within 7 months of onset. Most patients with CJD are between 50 and 75 years of age; however, patients as young as 12 and as old as 96 have been recorded. The role of prions in the pathogenesis of NDs is reviewed in Chap. 424.
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CJD is one malady in a group of disorders caused by prions composed of the prion protein (PrP). PrP prions reproduce by binding to the normal, cellular isoform of the prion protein (PrPC) and stimulating conversion of PrPC into the disease-causing isoform PrPSc. PrPC is rich in α-helix and has little β-structure, whereas PrPSc has less α-helix and a high amount of β-structure. The α-to-β structural transition in PrP is the fundamental event underlying this group of prion diseases (Table 438-1).
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