Skip to main content
PMC home page
Brain Pathology logoLink to Brain Pathology
. 2006 Apr 5;8(3):429–437. doi: 10.1111/j.1750-3639.1998.tb00165.x

Comparative Neuropathology of Kuru with the New Variant of Creutzfeldt‐Jakob Disease: Evidence for Strain of Agent Predominating Over Genotype of Host

CA McLean 1,✉, JW Ironside 2, MP Alpers 3, PW Brown 4, L Cervenakova 4, RMcD Anderson 1, CL Masters 1
PMCID: PMC8098151  PMID: 9669694

Abstract

The three major influences on the phenotype of the transmissible spongiform encephalopathies are believed to be strain of agent, route of infection and host genotype. We have compared the pathologic profiles and genotypes of the new variant of Creutzfeldt‐Jakob disease (vCJD) and kuru. The comparison reveals that there are distinct lesional differences particularly in the prion protein (PrP) load and distribution as seen by immunohistochemistry. The clinico‐pathologic phenotypes and the genotypes of these two diseases are sufficiently different to suggest that the strain of agent may play a greater role than any presumptive common route of peripherally acquired infection.

Full Text

The Full Text of this article is available as a PDF (217.6 KB).

References

  • 1. Alpers M (1968) Kuru: Implications of its transmissibility for the interpretation of its changing epidemiological pattern. In: Bailey OT, Smith DE, (Eds.), pp. 234–251. The Central Nervous System, Some Experimental Models of Neurological Diseases, International Academy of Pathology Monograph No 9. Williams and Wilkins: Baltimore , London , Sydney . [Google Scholar]
  • 2. Beck E and Daniel P (1979) Kuru and Creutzfeldt‐Jakob disease; Neuropathological lesions and their significance. In: Slow Transmissible Diseases of the Nervous System, Prusiner SB, Hadlow WJ, (Eds.), pp. 253–270, Academic Press: New York , London , Sydney , Toronto , San Francisco . [Google Scholar]
  • 3. Bell JE Neuropathological diagnosis of human prion disease. In: Methods in Molecular Medicine ‐ Prion Diseases, Baker HF, Ridley RM, (Eds.), Chapter 4, pp. 59–83, Humana Press: Totowa . [Google Scholar]
  • 4. Bell JE, Gentleman SM, Ironside JW, McCardle L, Lantos PL, Doey L, Lowe J, Fergusson J, Luthert P, McQuaid S, Allen IV (1997) Prion protein immunocytochemistry ‐ UK five centre consensus report. Neuropathol and Appl Neurobiol 23: 26–35. [PubMed] [Google Scholar]
  • 5. de Billette Villemeur TB, Deslys JP, Pradel A, Soubrie C, Alperovitch A, Tardieu M, Chaussain JL, Hauw JJ, Dormont D, Ruberg M and Agid Y (1996) Creutzfeldt‐Jakob disease from contaminated growth hormone extracts in France. Neurology 47: 690–695. [DOI] [PubMed] [Google Scholar]
  • 6. Bruce ME Strain typing studies of scrapie and BSE. In: Methods in Molecular Medicine ‐ Prion Diseases, Baker HF, Ridley RM, (Eds.), Chapter 13, pp. 223–235, Humana Press: Totowa . [Google Scholar]
  • 7. Bruce ME, Will RG, Ironside JW, McConnell, Drummond D, Suttle A, McCardle L, Chree A, Hope J, Birkett C, Cousens S, Fraser H, Bostock CJ (1997) Transmission to mice indicates that ‘new variant’ CJD is caused by the BSE agent. Nature 389: 498–501. [DOI] [PubMed] [Google Scholar]
  • 8. Budka H, Aguzzi A, Brown P, Brucher J‐P, Gugiani O, Gullotta F, Haltia M, Hauw J‐J, Ironside JW, Jellinger K, Kretzschmar HA, Lantos PL, Masullo C, Schlote WS, Tateishi J and Weller R (1995) Neuropathological diagnostic criteria for Creutzfeldt‐Jakob disease (CJD) and other human spongiform encephalopathies (prion diseases). Brain Pathol 5: 459–466. [DOI] [PubMed] [Google Scholar]
  • 9. Chesebro B. BSE AND Prions: Uncertainties about the agent (1998) Science 279:42–43. [DOI] [PubMed] [Google Scholar]
  • 10. Collinge J, Sidle KC, Meads J, Ironside J and Hill AF (1996) Molecular analysis of prion strain variation and the aetiology of ‘new variant’ CJD. Nature 383: 685–690. [DOI] [PubMed] [Google Scholar]
  • 11. Cousens SN, Vynnycky E, Zeidler M, Will RG Smith PG (1997) Predicting the CJD epidemic in humans. Nature 385: 197–198. [DOI] [PubMed] [Google Scholar]
  • 12. De Silva R, Ironside JW, McCardle L, Esmond T, Bell J, Will R, Windl O, Dempster M, Estibeiro P and Lathe R (1994) Neuropathological phenotype and ‘prion protein’ genotype correlation in sporadic Creutzfeldt‐Jakob disease. Neurosci Let 179: 50–52. [DOI] [PubMed] [Google Scholar]
  • 13. DeArmond SJ and Prusiner SB Prion diseases In: Greenfield's Neuropathology, Graham DI, Lantos PL, (Eds.), Chapter 5, pp. 235–280, Edward Arnold: London , Sydney , Auckland . [Google Scholar]
  • 14. Deslys J‐P, Marce D and Dormont D (1994) Similar genetic susceptibility in iatrogenic and sporadic Creutzfeldt‐Jakob disease. J Gen Virol 75: 23–27. [DOI] [PubMed] [Google Scholar]
  • 15. Fowler M and Robertson EG (1958) Observations on kuru. III: Pathological features in five cases. Australasian Ann Med 8: 16–26. [DOI] [PubMed] [Google Scholar]
  • 16. Hainfellner JA, Liberski PP, Guiroy DC, Cervenakova L, Brown P, Gajdusek DC and Budka H (1997) Pathology and immuncytochemistry of a kuru brain. Brain Pathol 7: 547–553. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17. Hainfellnner JA, Brantner‐Inthaler S, Cercenakova L, Brown P, Kitamoto T, Tateishi J, Diringer H, Libersi PP, Regele H, Feucht M, Mayr N, Wessley P, Summer K, Seitelberger F and Budka H (1995) The original Gerstmann‐Straussler‐Scheimker family of Austria: divergent clinico‐pathological phenotypes but constant PrP genotype. Brain Pathol 5: 201–213. [DOI] [PubMed] [Google Scholar]
  • 18. Hayward PAR, Bell JE and Ironside JW (1994) Prion protein immunochemistry: The development of reliable protocols for the investigation of Creutzfeldt‐Jakob disease. Neuropathol Appl Neurobiol 20: 375–383. [DOI] [PubMed] [Google Scholar]
  • 19. Hill AF, Desbruslais M, Joiner S, Sidle KCL, Gowland I, Collinge, Doey LJ, Lantos P. The same prion strain causes vCJD and BSE (1997) Nature 389:448–450. [DOI] [PubMed] [Google Scholar]
  • 20. Ironside JW New variant Creutzfeldt‐Jakob disease in the UK ‐ Clinical and pathological studies (1997) Brain Pathol 7:1243–1245. [Google Scholar]
  • 21. Ironside JW (1996) Review: Creutzfeldt‐Jakob disease. Brain Pathol 6:379–388. [DOI] [PubMed] [Google Scholar]
  • 22. Kitamoto T, Shin RW, Doh‐ure K, Tomokane N, Miyazono M, Muramoto T, Tatesi 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: 1285–1294. [PMC free article] [PubMed] [Google Scholar]
  • 23. Kakulas BA, Lecours AR and Gajdusek DC (1967) Further observations on the pathology of kuru. J Neuropathol Exp Neurol 26:85–97. [DOI] [PubMed] [Google Scholar]
  • 24. Klatzo I, Gajdusek DC and Zigas V (1959) Pathology of kuru. Lab Invest 8:799–847. [PubMed] [Google Scholar]
  • 25. Lantos P, Bhatia K, Doey LJ, AI‐Sarraj S, Doshi R, Beck J and Collinge J (1997) Is the neuropathology of new variant Creutzfeldt‐Jakob disease and kuru similar. Lancet 350: 187–188. [DOI] [PubMed] [Google Scholar]
  • 26. MacDonald ST, Sutherland K and Ironside JW (1996) Prion protein genotype and patholgical phenotype studies in sporadic Creutzfeldt‐Jakob disease. Neuropathol Appl Neurobiol 22: 285–292. [DOI] [PubMed] [Google Scholar]
  • 27. Masters CL, Gajdusek DC, Gibbs CJ (1981) Creutzfeldt‐Jakob disease virus isolations from the Gerstmann‐Sträussler Syndrome with an analysis of the various forms of amyloid plaque deposition in the virus‐induced spongiform encephalopathies Brain 104:594–588. [DOI] [PubMed] [Google Scholar]
  • 28. Masters CL, Richardson EP, Jr (1978) Subacute spongiform encephalopathy (Creutzfeldt‐Jakob disease) The nature and progression of spongiform changes. Brain 101:333–334. [DOI] [PubMed] [Google Scholar]
  • 29. Neumann MA, Gajdusek DC and Zigas V (1964) Neuropathological findings in exotic neurologic disorders among natives of the highlands of New Guinea. J Neuropath Exp Neurol 23:486–507. [DOI] [PubMed] [Google Scholar]
  • 30. Parchi P, Capellari S, Chen SG, Petersen RB, Gambetti P, Kopp N, Brown P, Kitamoto T, Tateishi J, Giese A, Kretzschmar H (1997) Typing prion isoforms. Nature 386:232–233. [DOI] [PubMed] [Google Scholar]
  • 31. Parchi P, Castellani R, Capellari S, Ghetti B, Young K, Chen SG, Farlow M, Dickson DW, Sima AAF, Trojanowski JQ, Petersen RB and Gambetti P (1996) Molecular basis of phenotypic variability in sporadic Creutzfeldt‐Jakob disease. Ann Neurol 39: 767–778. [DOI] [PubMed] [Google Scholar]
  • 32. Richardson EP and Masters CL (1995) The nosology of Creutzfeldt‐Jakob disease and conditions related to the accumulation of PrPCJD in the nervous system. Brain Pathol 5: 33–41. [DOI] [PubMed] [Google Scholar]
  • 33. Schulz‐Schaffer WJ, Giese A, Windl O and Kretzschmar HA (1996) Polymorphism at codon 129 of the prion protein gene determines cerebellar pathology in Creutzfeldt‐Jakob disease. Clin Neuropathol 15: 353–357. [PubMed] [Google Scholar]
  • 34. Shimizu H, Burns JC. PCR Strategies (1995) Academic Press, Inc. Innis MA, Gelfand DH, Sninsky JJ(Eds) pp 32–38. [Google Scholar]
  • 35. Weller RO, Steart PV and Powell‐Jackson JD (1986) Pathology of Creutzfeldt‐Jakob disease associated with pituitary‐derived human growth hormone administration. Neuropathol Appl Neurobiol 12: 117–129. [DOI] [PubMed] [Google Scholar]
  • 36. Wells GAH and Wilesmith JW (1995) The neuropathology and epidemiology of bovine spongiform encephalopathy. Brain Pathol 5:91–103. [DOI] [PubMed] [Google Scholar]
  • 37. Will RG, Ironside JW, Zeidler M, Cousens SN, Estibeiro K, Alperovitch A, Poser S, Pocchiari M, Hofman A (1996) A new variant of Creutzfeldt‐Jakob disease in the UK. Lancet 347: 921–25. [DOI] [PubMed] [Google Scholar]

Articles from Brain Pathology are provided here courtesy of Wiley

RESOURCES