Human prion diseases

  • J. W. Ironside
Part of the Journal of Neural Transmission Supplement book series (NEURAL SUPPL, volume 47)


The classical prion diseases in man comprise Creutzfeldt-Jakob disease (CJD), Kuru and Gerstmann-Sträussler-Scheinker syndrome (GSS). Recent advances in the biochemistry and the molecular biology of the transmissible agents responsible for these human spongiform encephalopathies have prompted renewed interest in their clinical and pathological features. A broadening spectrum of human prion diseases has now been identified including novel entities such as Fatal Familial Insomnia and variants of CJD and GSS characterised by specific abnormalities in the human prion protein (PrP) gene on chromosome 20. Accumulation of PrP in the central nervous system is a characteristic feature of all these disorders, although the relationship between PrP localisation, classical neuropathology, clinical features and genotype still requires clarification. A national surveillance project for CJD was established in 1990 in the United Kingdom in order to assess the possible implications of bovine spongiform encephalopathy for human health. The identification of an apparently new variant of CJD in young patients in UK raises the possibility of such a link; further studies are required to assess the significance of this observation.


Prion Protein Prion Disease Bovine Spongiform Encephalopathy Inclusion Body Myositis Fatal Familial Insomnia 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Advisory Committee on Dangerous Pathogens (1994) Precautions for work with human and animal tranmissible spongiform encephalopathies, 1st edn. HMSO, LondonGoogle Scholar
  2. Amouyel P, Vidal O, Launay JM, Laplanche JL (1994) The apolipoprotein E alleles as major susceptibility factors for Creutzfeldt-Jakob disease. Lancet 344: 1315–1318Google Scholar
  3. Anonymous (1990) Prion disease - spongiform encephalopathies unveiled. Lancet 336: 21–22CrossRefGoogle Scholar
  4. Askanas V, King EW, Alverez RB (1992) Light and electron microscopic localisation of (3-amyloid protein in muscle biopsies of patients with inclusion-body myositis. Am J Pathol 141: 31–36PubMedGoogle Scholar
  5. Askanas V, Bilak M, Engel WK, Alvarez RB, Tome F, Leclerc A (1993) Prion protein is abnormally accumulated in inclusion-body myositis. Neuro Report 5: 25–28Google Scholar
  6. Baker HF, Ridley RM (1992) The genetics and transmissibility of human spongiform encephalopathy. Neurodegen 1: 3–16Google Scholar
  7. Bastian FO (ed) (1991) Creutzfeldt-Jakob disease and other transmissible human spongiform encephalopathies. Mosby Year Book, St LouisGoogle Scholar
  8. Bell JE, Ironside JW (1993a) Neuropathology of spongiform encephalopathies in humans. Br Med Bull 49: 738–777Google Scholar
  9. Bell JE, Ironside JW (1993b) How to tackle a possible Creutzfeldt-Jakob disease necropsy. J Clin Pathol 46: 193–197CrossRefGoogle Scholar
  10. Bradley R, Wilesmith JW (1993) Epidemiology and control of bovine spongiform encephalopathy (BSE). Br Med Bull 49: 932–959PubMedGoogle Scholar
  11. Brown P, Wolff A, Gajdusek DC (1990) A simple and effective method for inactivating virus infectivity in formalin-fixed tissue samples from patients with Creutzfeldt-Jakob disease. Neurology 40: 887–90PubMedGoogle Scholar
  12. Brown P, Preece MA, Will RG (1992) “Friendly fire” in medicine: hormones homografts and Creutzfeldt-Jakob disease. Lancet 340: 24–27PubMedCrossRefGoogle Scholar
  13. Brown P, Crevenakova L, Boellaard JW, Stavrou D, Goldfarb LG, Gajdusek DC (1994) Identification of a PRNP gene mutation in Jakob’s original Creutzfeldt-Jakob disease family. Lancet 344: 130–131PubMedCrossRefGoogle Scholar
  14. Budka H, Aguzzi A, Brown P, Brucher J-M, Bugiani O, Gullotta F, Haltia M, Hauw J-J, Ironside JW, Jellinger K, Kretzschmar HA, Lantos PL, Masullo C, Scholte W, Tateishi J, Weller RO (1995) Neuropathological diagnostic criteria for CreutzfeldtJakob disease (CJD) and other human spongiform encephalopathies (prion diseases). Brain Pathol 5: 459–465PubMedCrossRefGoogle Scholar
  15. Bugiani O, Giaccone G, Verga L, Pollo B, Frangione B, Farlow MR, Tagliavini F, Ghetti B (1993) (3PP participates in PrP-amyloid plaques of Gerstmann-Sträussler-Scheinker disease, Indiana kindred. J Neuropathol Exp Neurol 52: 66–70CrossRefGoogle Scholar
  16. Collinge J, Owen F, Poulter M, Leach M, Crow TJ, Rossor MN, Mullan MJ, Janota I, Lantos PL (1990) Prion dementia without characteristic pathology. Lancet 336: 7–9PubMedCrossRefGoogle Scholar
  17. Collinge J, Palmer MS, Dryden AJ (1991) Genetic predisposition to iatrogenic Creutzfeldt-Jakob disease. Lancet 337: 1441–42PubMedCrossRefGoogle Scholar
  18. Collinge J, Palmer MS, Sidle KCL, Gowland I, Medori R, Ironside JW, Lantos P (1995) Tranmission of fatal familial insomnia to laboratory animals. Lancet 346: 569–570PubMedCrossRefGoogle Scholar
  19. Creutzfeldt HG (1920) Über eine eigenartige herdförmige Erkrankung des Zentralnervensystems. Z Ges Neurol Psychiat 57: 1–18CrossRefGoogle Scholar
  20. De Silva R, Ironside JW, McCardle L, Esmonde T, Bell JE, Will RG, Windle O, Dempster M, Estibeiro P, Lathe R (1994) Neuropathological phenotype and “prion protein” genotype correlation in sporadic Creutzfeldt-Jakob disease. Neurosci Lett 179: 50–52PubMedCrossRefGoogle Scholar
  21. DeArmond SJ (1993) Alzheimer’s disease and Creutzfeldt-Jakob disease: overlap of pathogenic mechanisms. Curr Opin Neurol 6: 872–881PubMedCrossRefGoogle Scholar
  22. Delasnerie-Laupretre N, Poser S, Pocchiari M, Wientjens DPW, Will R (1995) Creutzfeldt-Jakob disease in Europe. Lancet 346: 898PubMedCrossRefGoogle Scholar
  23. Frasier SD, Foley Jr TP (1994) Creutzfeldt-Jakob disease in recipients of pituitary hormones. J Clin Endocrinol Metabol 78: 1277–1279CrossRefGoogle Scholar
  24. Gajdusek DC, Zigas V (1957) Degenerative disease of the central nervous system in New Guinea. The endemic occurrence of “kuru” in the native population. N Engl J Med 257: 974–978PubMedCrossRefGoogle Scholar
  25. Gajdusek DC, Gibbs CJ, Alpers MP (1966) Experimental transmission of a kuru-like syndrome in chimpanzees. Nature 209: 794–796PubMedCrossRefGoogle Scholar
  26. Gambetti P, Peterson R, Monari L, Tabaton M, Autillo-Gambetti L, Cortelli P, Montagna P, Lugaresi E (1993) Fatal familial insomnia and the widening spectrum of prion diseases. Br Med Bull 49: 980–994PubMedGoogle Scholar
  27. Gerstmann J, Sträussler E, Scheinker I (1936) Über eine eigenartige hereditär-familiäre Erkrankung des Zentralnervensystems, zugleich ein Beitrag zur Frage des vorzeitigen lokalen Alterns. Z Neurol Psych 154: 736–762CrossRefGoogle Scholar
  28. Gibbs CJ, Gajdusek DC, Asher DM, Alpers MP, Beck E, Daniel PM, Matthews WB (1968) Creutzfeldt-Jakob disease (subacute spongiform encephalopathy): transmission to the chimpanzee. Science 161: 388–389PubMedCrossRefGoogle Scholar
  29. Goldfarb LG, Brown P, Cervenakova L, Gajdusek CJ (1994) Molecular genetic studies of Creutzfeldt-Jakob disease. Mol Neurobiol 8: 89–97PubMedCrossRefGoogle Scholar
  30. Goodbrand IA, Ironside JW, Nicolson D, Bell JE (1995) Prion protein accumulation in the spinal cords of patients with sporadic and growth hormone associated Cruetzfeldt-Jakob disease. Neurosci Lett 183: 127–130PubMedCrossRefGoogle Scholar
  31. Hainfellner JA, Brantner-Inthaler S, Cercenakova L, Brown P, Kitamoto T, Tateishi J, Diringer H, Liberski PP, Regele H, Feucht M, Mayr N, Wessely P, Summer K, Seitelberger F, Budka H (1995) The original Gerstmann-Sträussler-Scheinker family of Austria: divergent clinicopathological phenotypes but constant PrP genotype. Brain Pathol 5: 201–213PubMedCrossRefGoogle Scholar
  32. Hansen LA, Masliah E, Terry RD, Mirra SS (1989) A neuropathological subset of Alzheimer’s disease with concomitant Lewy body disease and spongiform change. Acta Neuropathol 78: 194–201PubMedCrossRefGoogle Scholar
  33. Hayward PAR, Bell JE, Ironside JW (1994) Prion protein immunocytochemistry: the development of reliable protocols for the investigation of Creutzfeldt-Jakob disease. Neuropathol Appl Neurobiol 20: 375–383PubMedCrossRefGoogle Scholar
  34. Hsiao KK, Doh-ura K, Kitamoto T, Tateishi J, Prusiner SB (1989) A prion protein amino acid substitution in ataxic Gerstmann-Sträussler syndrome. Ann Neurol 26: 137Google Scholar
  35. Jakob A (1921) Über eigenartige Erkrankungen des Zentralnervensystems mit bemerkenswertem anatomischen Befunden (Spastische PseudoskleroseEncephalomyelopathie mit disseminierten Degenerationsherden). Z Ges Neurol Psychiat 64: 147–228CrossRefGoogle Scholar
  36. Jendroska K, Hoffmann O, Schelosky L, Lees AJ, Poewe W, Daniel SE (1994) Absence of disease related prion protein in neurodegenerative disorders presenting with Parkinson’s syndrome. J Neurol Neurosurg Psychiatry 57: 1249–1251PubMedCrossRefGoogle Scholar
  37. Kitamoto T, Shin RW, Doh-ura K, Tomokane N, Miyazono M, Muramoto T, Tateishi J (1992) Abnormal isoform of prion protein accumulates in the synaptic structures of the central nervous system in patients with Creutzfeldt-Jakob Disease. Am J Pathol 140: 1285–129PubMedGoogle Scholar
  38. Klatzo I, Gajdusek DC, Vigas V (1959) Pathology of kuru. Lab Invest 8: 799–847 Lugaresi E, Medori R, Montagna P, Baruzzi A, Cortelli P, Lugaresi A, Tinuper P, Zucconi M, Gambett P (1986) Fatal familial insomnia and dysautonomia with selective degeneration of thalamic nuclei. N Engl J Med 315: 997–1003Google Scholar
  39. Martinez-Lage JF, Poza M, Sola J, Tortosa JG, Brown P, Crevenakova L, Esteban JA, Mendoza A (1994) Accidental transmission of Creutzfeldt-Jakob disease by dural cadaveric grafts. J Neurol Neurosurg Psychiatry 57: 1091–1904PubMedCrossRefGoogle Scholar
  40. Masters CL, Richardson EP (1978) Subacute spongiform encephalopathy (CreutzfeldtJakob disease). The nature and progression of spongiform change. Brain 101: 333–334PubMedCrossRefGoogle Scholar
  41. Masters CL, Gajdusek DC, Gibbs CJ (1981) Creutzfeldt-Jakob disease: virus isolates from the Gerstmann-Sträussler syndrome. Brain 104: 559–588PubMedCrossRefGoogle Scholar
  42. Medori R, Tritschler JH, LeBlanc A, Villare F, Manetto V, Ghen HY, Xuf R, Leal S, Montagna P, Cortelli P, Tinuper P, Avoni P, Mochi M, Baruzzi A, Hauw JJ, Ott J, Lugarest E, Autilio-Gambettia L, Gambetti P (1992) Fatal familial insomnia, a prion disease with a mutation at codon 178 of the prion protein gene. N Engl J Med 7: 444–449CrossRefGoogle Scholar
  43. Metters JS (1990) Neuro and ophthalmic surgery procedures in patients with or suspected to have or at risk of developing CJD or GSS. Letter PL(92)CO/4 to Consultants and Health Managers, Department of Health, LondonGoogle Scholar
  44. Neumann MA, Gajdusek DC, Vigas V (1965) Neuropathologie findings in exotic neurologic disorders among natives of the highlands of New Guinea. J Neuropathol Exp Neurol 18: 486–507Google Scholar
  45. Nieto A, Goldfarb LG, Brown P, McCombie WR, Trapp S, Asher DM, Gajdusek DC (1991) Codon 178 mutation in ethnically diverse Creutzfeldt-Jakob disease families. Lancet 337: 622–623PubMedCrossRefGoogle Scholar
  46. Petersen RB, Tabaton M, Chen SG, Monari L, Richardson SL, Lynches T, Manetto V, Lanska DJ, Markesbery WR, Currier RD, Autilio-Gambetti L, Wilhelmsen KC, Gambetti P (1995) Familial progessive subcortical gliosis: presence of prions and linkage to chromosome 17. Neurology 45: 1062–1067PubMedGoogle Scholar
  47. Pickering-Brown SM, Mann DMA, Owen F, Ironside JW, de Silva R, Roberts DA, Balderson DJ, Cooper PN (1995) Allelic variations in apolipoprotein E and prion protein genotype related to plaque formation and age of onset in sporadic Creutzfeldt-Jakob disease. Neurosci Lett 187: 127–129Google Scholar
  48. Prusiner S B (1994) Biology and genetics of prion disease. Ann Rev Microbiol 48: 655–686CrossRefGoogle Scholar
  49. Richardson EP Jn, Masters CL (1995) The nosology of Creutzfeldt-Jakob disease and conditions related to the accumulation of PrPcm in the nervous system. Brain Pathol 5: 33–41PubMedCrossRefGoogle Scholar
  50. Smith PEM, Zeidler M, Ironside JW, Estibeiro P, Moss TH (1995) Creutzfeldt-Jakob disease in a dairy farmer. Lancet 346: 898PubMedCrossRefGoogle Scholar
  51. Wells GAH, Scott AC, Johnson CT, Gunning RF, Hancock RD, Jeffrey M, Dawson M, Bradley R (1987) A novel progressive spongiform encephalopathy in cattle. Vet Rec 121: 419–420PubMedCrossRefGoogle Scholar
  52. Westaway D, DeArmond SJ, Cayetano-Canlas J, Groth D, Foster D, Yang S, Torchia M, Carlson GA, Prusiner SB (1994) Degeneration of skeletal muscle, peripheral nerves and the central nervous system in transgenic mice overexpressing wild-type prion proteins. Cell 76: 117–129PubMedCrossRefGoogle Scholar
  53. Will RG (1991) The spongiform encephalopathies. J Neurol Neurosurg Psychiatry 54: 761–763PubMedCrossRefGoogle Scholar
  54. Will RG (1993) Epidemiology of Creutzfeldt-Jakob disease. Br Med Bull 49: 960–970PubMedGoogle Scholar
  55. Will RG, Ironside JW, Zeidler M, Estibeiro K, Alperovitch A, Poser S, Pocchiari M, Hofman A, Smith PG (1996) A new variant of Creutzfeldt-Jakob disease in the UK. Lancet 347: 921–925PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • J. W. Ironside
    • 1
  1. 1.Neuropathology Laboratory, Department of PathologyThe University of Edinburgh, Western General HospitalEdinburghUK

Personalised recommendations