Creutzfeldt-Jakob Disease: Causes

Pathogenesis (disease development)

According to the prion hypothesis, the prion is thought to arise from an infectious form of a misfolded protein. It is expressed primarily cells of the nervous system. The propagation of prions occurs by transforming the anti-helix structure of the proteins. The change in structure results in the formation of amyloid plaques and spongy remodeling of brain tissue.

The new variant of lethal (fatal) Creutzfeldt-Jakob disease (now known as “new variant Creutzfeldt-Jakob disease” (nvCJD)) is thought to be caused in humans by consumption of BSE-contaminated beef.

Etiology (Causes)

Genetically determined prion diseases

Biographic causes

  • Genetic burden from parents, grandparents in the genetic form of CJD – they are all autosomal dominant inherited with almost 100% penetrance

Sporadic prion diseases

  • The trigger is not known

New variant of Creutzfeldt-Jakob disease (nvCJD)

Biographic causes

  • Genetic factors:
    • Genetic risk reduction depending on gene polymorphisms:
      • Genes/SNPs (single nucleotide polymorphism):
        • Gene: PRNP
        • SNP: rs1799990 in gene PRNP
          • Allele constellation: AA (getting nvCJD is possible) [methionine homozygous] (40% of cases in the population).
          • Allele constellation: AG (getting nvCJD is possible but very unlikely) [methionine/valine heterozygous].
          • Allele constellation: GG (resistant to nvCJD).

Note: All nCJD patients documented so far (about 230 worldwide) were homozygous for methionine. Now, for the first time after a long incubation period, a diseased person with methionine/valine has emerged.

Behavioral causes

  • Ingestion of infected food – beef and beef derived products.

Iatrogenic form of CJD

Other causes

  • Transmission from infected body donations or infected surgical instrumentation.
  • Transmission through blood and blood products