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At a glance

A rapidly progressive, universally fatal neurodegenerative prion (PrP; acronym that stands for “Proteinaceous Infectious Particles” or simply “Prion Protein”) disorder, which belongs to a group of diseases known as transmissible spongiform encephalopathies.

Synonyms

Corticostriatal Spinal Degeneration; Subacute Spongiform Encephalopathy; Infectious Spongiform Encephalopathy; Spastic Pseudosclerosis.

Incidence

Worldwide, the overall incidence (for all types combined) of Creutzfeldt-Jakob disease (CJD) in the general population is approximately 0.5-1.5:1,000,000 per year. Around 350 cases are diagnosed in the United States every year. Both genders are equally affected. Three forms of CJD can be distinguished: a sporadic form that accounts for about 85% of all cases, a genetic or familial form accounting for 10 to 15%, and an acquired form that accounts for less than 1% of all cases. A variant of the acquired form (vCJD) is related to consumption of animal products “infected” with BSE (Bovine Spongiform Encephalopathy, also known as “Mad cow disease” or “Scrapie” in sheep and goats), which mainly occurred in the United Kingdom (and to a lesser degree in France). A causal association between vCJD and BSE is supported by epidemiologic and laboratory evidence in areas with a high prevalence of BSE and the lack thereof in basically BSE-free regions. A higher risk for vCJD is expected for patients who received blood components, organs, or other tissues from donors who subsequently developed vCJD. Iatrogenic transmission (eg, during surgery from improper sterilized equipment) is also possible, with the first case reported in 1974. The “infectious” agent in prion disease consists almost entirely of a host-encoded protease-resistant, neuronal cell surface sialoglycoprotein termed prion protein.

Genetic inheritance

Autosomal dominant for the genetic/familial form. The defect is caused by mutations in the PRNP (Prion Protein, PrP) gene located on chromosome 20p13. The cause for the sporadic form is unknown, but could be the result of other (somatic) mutations that render PrP susceptible to the same changes seen in PrP in the familial form of CJD (see “Pathophysiology”).

Pathophysiology

The cause and pathophysiology are still not fully understood, more than 20 years after Stanley Prusiner received the Nobel Prize in Medicine (1997) for his contributions in elucidating the pathogenesis of CJD. Prusiner postulated that the elusive transmissible “agent” causing the spongiform encephalopathy was in fact a misfolded variation of the regular prion protein (PrP) normally present on the surface of neurons and required for normal synaptic function. He labeled the different forms of the prion protein PrPC (the normal PrP) and PrPCJD (the pathologic variant causing CJD). While chemically similar, misfolding of PrPC leads to PrPCJD with widely different chemical properties, rendering it insoluble in water and highly resistant to breakdown by cellular proteases, regular clinical viral inactivation, or sterilization processes. The misfolding of PrP...

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