CHAPTER 40: PRION DISEASES

INTRODUCTION

Prions are proteins that adopt an alternative conformation, which becomes self-propagating. Some prions cause degeneration of the central nervous system (CNS). Once relegated to causing a group of rare disorders of the CNS such as Creutzfeldt-Jakob disease (CJD), prions—as mounting evidence shows—also appear to play a key role in more common illnesses such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). While CJD is caused by the accumulation of PrP^Sc, increasing data argue that Aβ prions cause AD, α-synuclein prions cause PD, and tau prions cause the frontotemporal dementias (FTDs). In this chapter, we confine our discussion to CJD, which typically presents with a rapidly progressive dementia as well as motor abnormalities. The illness is relentlessly progressive and generally causes death within 9 months of onset. Most CJD patients are between 50 and 75 years of age; however, patients as young as 17 and as old as 83 have been recorded.

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 (PrP^C) and stimulating conversion of PrP^C into the disease-causing isoform PrP^Sc. PrP^C is rich in α-helix and has little β-structure, whereas PrP^Sc has less α-helix and a high amount of β-structure (Fig. 40-1). This α-to-β structural transition in PrP is the fundamental event underlying this group of prion diseases (Table 40-1).