Current Infectious Disease Reports

, Volume 6, Issue 4, pp 305–315 | Cite as

Prion diseases: Update on mad cow disease, variant creutzfeldt-jakob disease, and the transmissible spongiform encephalopathies

  • Jacqueline Janka
  • Frank Maldarelli


Transmissible spongiform encephalopathies (TSEs) are a group of progressive, fatal neurodegenerative disorders that share a common spongiform histopathology. TSEs may be transmitted in a sporadic, familial, iatrogenic, or zoonotic fashion. The putative infectious agent of TSE, the prion, represents a novel paradigm of infectious disease with disease transmission in the absence of nucleic acid. Several small but spectacular epidemics of TSEs in man have prompted widespread public health and food safety concerns. Although TSEs affect a comparatively small number of individuals, prion research has revealed fascinating insights of direct relevance to common illnesses. This paper reviews recent advances that have shed new light on the nature of prions and TSEs.


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References and Recommended Reading

  1. 1.
    Aguzzi A, Polymenidou M: Mammalian prion biology: one century of evolving concepts. Cell 2004, 116:313–327.PubMedCrossRefGoogle Scholar
  2. 2.
    The spread of mad cow disease. HEALTH/12/23/madcow.chronology.reut/index.html. Accessed June 2, 2004.Google Scholar
  3. 3.
    Pattison IH, Jones KM: The possible nature of the transmissible agent of scrapie. Vet Rec 1967, 80:2–9.PubMedGoogle Scholar
  4. 4.
    Prusiner SB: Novel proteinaceous infectious particles cause scrapie. Science 1982, 216:136–144.PubMedCrossRefGoogle Scholar
  5. 5.
    Calzolai L, Lysek DA, Guntert P, et al.: NMR structures of three single-residue variants of the human prion protein. Proc Natl Acad Sci U S A 2000, 97:8340–8345.PubMedCrossRefGoogle Scholar
  6. 6.
    Ma J, Lindquist S: Conversion of PrP to a self-perpetuating PrPSc-like conformation in the cytosol. Science 2002, 298:1785–1788.PubMedCrossRefGoogle Scholar
  7. 7.
    Pan KM, Baldwin M, Nguyen J, et al.: Conversion of alpha-helices into beta-sheets features in the formation of the scrapie prion proteins. Proc Natl Acad Sci U S A 1993, 90:10962–10966.PubMedCrossRefGoogle Scholar
  8. 8.
    Prusiner SB: Prions. Proc Natl Acad Sci U S A 1998, 95:13363–13383.PubMedCrossRefGoogle Scholar
  9. 9.
    Millhauser GL: Copper binding in the prion protein. Acc Chem Res 2004, 37:79–85.PubMedCrossRefGoogle Scholar
  10. 10.
    Roucou X, Gains M, LeBlanc AC: Neuroprotective functions of prion protein. J Neurosci Res 2004, 75:153–161.PubMedCrossRefGoogle Scholar
  11. 11.
    Caughey B: Transmissible spongiform encephalopathies, amyloidoses and yeast prions: common threads? Nat Med 2000, 6:751–754.PubMedCrossRefGoogle Scholar
  12. 12.
    King CY, Diaz-Avalos R: Protein-only transmission of three yeast prion strains. Nature 2004, 428:319–323. This is a critical test of the protein-only prion hypothesis.PubMedCrossRefGoogle Scholar
  13. 13.
    Tanaka M, Chien P, Naber N, et al.: Conformational variations in an infectious protein determine prion strain differences. Nature 2004, 428:323–328. s is a critical test of the protein-only prion hypothesisPubMedCrossRefGoogle Scholar
  14. 14.
    Hetz C, Russelakis-Carneiro M, Maundrell K, et al.: Caspase-12 and endoplasmic reticulum stress mediate neurotoxicity of pathological prion protein. EMBO J 2003, 22:5435–5445.PubMedCrossRefGoogle Scholar
  15. 15.
    Walz R, Castro RM, Velasco TR, et al.: Surgical outcome in mesial temporal sclerosis correlates with prion protein gene variant. Neurology 2003, 61:1204–1210.PubMedGoogle Scholar
  16. 16.
    Collins SJ, Lawson VA, Masters CL: Transmissible spongiform encephalopathies. Lancet 2004, 363:51–61.PubMedCrossRefGoogle Scholar
  17. 17.
    Beisel CE, Morens DM: Variant Creutzfeldt-Jakob disease and the acquired and transmissible spongiform encephalopathies. Clin Infect Dis 2004, 38:697–704.PubMedCrossRefGoogle Scholar
  18. 18.
    Zerr I, Pocchiari M, Collins S, et al.: Analysis of EEG and CSF 14-3-3 proteins as aids to the diagnosis of Creutzfeldt-Jakob disease. Neurology 2000, 55:811–815.PubMedGoogle Scholar
  19. 19.
    Gambetti P, Kong Q, Zou W, et al.: Sporadic and familial CJD: classification and characterisation. Br Med Bull 2003, 66:213–239.PubMedCrossRefGoogle Scholar
  20. 20.
    Montagna P, Cortelli P, Avoni P, et al.: Clinical features of fatal familial insomnia: phenotypic variability in relation to a polymorphism at codon 129 of the prion protein gene. Brain Pathol 1998, 8:515–520.PubMedCrossRefGoogle Scholar
  21. 21.
    Lugaresi E, Medori R, Montagna P, et al.: Fatal familial insomnia and dysautonomia with selective degeneration of thalamic nuclei. N Engl J Med 1986, 315:997–1003.PubMedCrossRefGoogle Scholar
  22. 22.
    Monari L, Chen SG, Brown P, et al.: Fatal familial insomnia and familial Creutzfeldt-Jakob disease: different prion proteins determined by a DNA polymorphism. Proc Natl Acad Sci U S A 1994, 91:2839–2842.PubMedCrossRefGoogle Scholar
  23. 23.
    Montagna P, Gambetti P, Cortelli P, Lugaresi E: Familial and sporadic fatal insomnia. Lancet Neurol 2003, 2:167–176.PubMedCrossRefGoogle Scholar
  24. 24.
    Bugiani O, Giaccone G, Piccardo P, et al.: Neuropathology of Gerstmann-Straussler-Scheinker disease. Microsc Res Tech 2000, 50:10–15.PubMedCrossRefGoogle Scholar
  25. 25.
    Brown P, Preece M, Brandel JP, et al.: Iatrogenic Creutzfeldt-Jakob disease at the millennium. Neurology 2000, 55:1075–1081.PubMedGoogle Scholar
  26. 26.
    Gajdusek DC, Zigas V: Degenerative disease of the central nervous system in New Guinea; the endemic occurrence of kuru in the native population. N Engl J Med 1957, 257:974–978.PubMedCrossRefGoogle Scholar
  27. 27.
    Mead S, Stumpf MP, Whitfield J, et al.: Balancing selection at the prion protein gene consistent with prehistoric kurulike epidemics. Science 2003, 300:640–643.PubMedCrossRefGoogle Scholar
  28. 28.
    Coffin J, Hughes SH, Varmus H: Retroviruses. New York: Cold Spring Harbor Laboratory Press; 1997.Google Scholar
  29. 29.
    Wells GA, Scott AC, Johnson CT, et al.: A novel progressive spongiform encephalopathy in cattle. Vet Rec 1987, 121:419–420. s is the initial description of BSEPubMedGoogle Scholar
  30. 30.
    BSE Inquiry--the final stage. static/special_report/1999/06/99/bse_inquiry/default.stm. Accessed June 2, 2004.Google Scholar
  31. 31.
    Kapur N, Abbott P, Lowman A, Will RG: The neuropsychological profile associated with variant Creutzfeldt-Jakob disease. Brain 2003, 126:2693–2702.PubMedCrossRefGoogle Scholar
  32. 32.
    Collie DA, Summers DM, Sellar RJ, et al.: Diagnosing variant Creutzfeldt-Jakob disease with the pulvinar sign: MR imaging findings in 86 neuropathologically confirmed cases. AJNR Am J Neuroradiol 2003, 24:1560–1569. This is a review of MRI findings in vCJD.PubMedGoogle Scholar
  33. 33.
    Hill AF, Butterworth RJ, Joiner S, et al.: Investigation of variant Creutzfeldt-Jakob disease and other human prion diseases with tonsil biopsy samples. Lancet 1999, 353:183–189.PubMedCrossRefGoogle Scholar
  34. 34.
    Will RG, Ironside JW, Zeidler M, et al.: A new variant of Creutzfeldt-Jakob disease in the UK. Lancet 1996, 347:921–925. This is the initial description of vCJD.PubMedCrossRefGoogle Scholar
  35. 35.
    Hill AF, Desbruslais M, Joiner S, et al.: The same prion strain causes vCJD and BSE. Nature 1997, 389:448–450, 526. This article provides biochemical evidence linking BSE and vCJD.PubMedCrossRefGoogle Scholar
  36. 36.
    Herzog C, Sales N, Etchegaray N, et al.: Tissue distribution of bovine spongiform encephalopathy agent in primates after intravenous or oral infection. Lancet 2004, 363:422–428.PubMedCrossRefGoogle Scholar
  37. 37.
    Glatzel M, Abela E, Maissen M, Aguzzi A: Extraneural pathologic prion protein in sporadic Creutzfeldt-Jakob disease. N Engl J Med 2003, 349:1812–1820.PubMedCrossRefGoogle Scholar
  38. 38.
    In-depth discussion of variant Creutzfeld-Jacob disease and blood donation. blood/supply/cjdv.html. Accessed April 12, 2004.Google Scholar
  39. 39.
    Llewelyn CA, Hewitt PE, Knight RS, et al.: Possible transmission of variant Creutzfeldt-Jakob disease by blood transfusion. Lancet 2004, 363:417–421.PubMedCrossRefGoogle Scholar
  40. 40.
    Probable variant Creutzfeldt-Jakob disease in a U.S. resident-Florida, 2002. MMWR Morb Mortal Wkly Rep 2002, 51:927–929.Google Scholar
  41. 41.
    Veneman announces expanded BSE surveillance program. Accessed March 31, 2004.Google Scholar
  42. 42.
    Salman MD: Chronic wasting disease in deer and elk: scientific facts and findings. J Vet Med Sci 2003, 65:761–768.PubMedCrossRefGoogle Scholar
  43. 43.
    Fatal degenerative neurologic illnesses in men who participated in wild game feasts--Wisconsin, 2002. MMWR Morb Mortal Wkly Rep 2003, 52:125–127.Google Scholar
  44. 44.
    Belay ED, Williams ES, Miller MW, et al.: Chronic wasting disease and potential transmission to humans. Emerg Infect Dis 2004, In press.Google Scholar
  45. 45.
    Van Everbroeck B, Quoilin S, Boons J, et al.: A prospective study of CSF markers in 250 patients with possible Creutzfeldt-Jakob disease. J Neurol Neurosurg Psychiatr 2003, 74:1210–1214.PubMedCrossRefGoogle Scholar
  46. 46.
    Collie DA, Sellar RJ, Zeidler M, et al.: MRI of Creutzfeldt-Jakob disease: imaging features and recommended MRI protocol. Clin Radiol 2001, 56:726–739.PubMedCrossRefGoogle Scholar
  47. 47.
    Schroter A, Zerr I, Henkel K, et al.: Magnetic resonance imaging in the clinical diagnosis of Creutzfeldt-Jakob disease. Arch Neurol 2000, 57:1751–1757.PubMedCrossRefGoogle Scholar
  48. 48.
    Martindale J, Geschwind MD, De Armond S, et al.: Sporadic Creutzfeldt-Jakob disease mimicking variant Creutzfeldt-Jakob disease. Arch Neurol 2003, 60:767–770.PubMedCrossRefGoogle Scholar
  49. 49.
    Mallucci G, Dickinson A, Linehan J, et al.: Depleting neuronal PrP in prion infection prevents disease and reverses spongiosis. Science 2003, 302:871–874.PubMedCrossRefGoogle Scholar
  50. 50.
    Heppner FL, Musahl C, Arrighi I, et al.: Prevention of scrapie pathogenesis by transgenic expression of anti-prion protein antibodies. Science 2001, 294:178–182.PubMedCrossRefGoogle Scholar
  51. 51.
    Questions and answers regarding Creutzfeldt-Jakob disease infection-control practices. cjd/cjd_inf_ctrl_qa.htm. Accessed June 2, 2004.Google Scholar

Copyright information

© Current Science Inc. 2004

Authors and Affiliations

  • Jacqueline Janka
  • Frank Maldarelli
    • 1
  1. 1.NCI, National Institutes of HealthBethesdaUSA

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