Prion Diseases pp 173-180 | Cite as

Detection of PrPSc in subclinical BSE with the paraffin-embedded tissue (PET) blot

  • W. J. Schulz-Schaeffer
  • R. Fatzer
  • M. Vandevelde
  • H. A. Kretzschmar
Part of the Archives of Virology. Supplementa book series (ARCHIVES SUPPL, volume 16)


The appearance of a new variant of CJD (vCJD) in young patients has caused considerable public concern and there is evidence that this novel disease is caused by the same agent as BSE. BSE is a prion disease that became epidemic in the UK, with a peak incidence in January 1993. New test systems should aim to identify BSE-infected cattle early in the incubation period. We compared the established histological and im-munohistochemical methods and the Western blot method used by Prionics with the PET blot method that detects prion PrPSc deposits in formalin-fixed and paraffin-embedded tissue. Investigating the obex region with the PET blot, all BSE cases were detectable and no false positive cases occurred. From the Swiss culling program, five clinically healthy cattle out of 1761 were identified as incubating BSE. With the PET blot method four of them showed the same PrPSc deposition pattern that was seen in clinical BSE, though less conspicuous. In one of the five cases, PrPSc was restricted to two brain stem nuclei, a pattern that was reported to be the first manifestation of PrPSc deposits in the brain after peripheral infection and one that occurs after half of the incubation time. In this case, histology and Western blot were negative.


Prion Disease Bovine Spongiform Encephalopathy Dorsal Motor Nucleus Western Blot Method Solitary Tract Nucleus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Anderson RM, Donnelly CA, Ferguson NM, Woolhouse MEJ, Watt CJ, Udy HJ, MaWhinney S, Dunstan SP, Southwood TRE, Wilesmith JW, Ryan JBM, Hoinville LJ, Hillerton JE, Austin AR, Wells GAH (1996) Transmission dynamics and epidemiology of BSE in British cattle. Nature 382: 779–788PubMedCrossRefGoogle Scholar
  2. 2.
    Anonymous (1999) BSE Enforcement Bulletin. See website: http://www. maff. gov. uk/maffhome. htm, 33: 1–22Google Scholar
  3. 3.
    Baldauf E, Beekes M, Diringer H (1997) Evidence for an alternative direct route of access for the scrapie agent to the brain bypassing the spinal cord. J Gen Virol 78: 1187–1197PubMedGoogle Scholar
  4. 4.
    Beekes M, McBride PA, Baldauf E (1998) Cerebral targeting indicates vagal spread of infection in hamsters fed with scrapie. J Gen Virol 79: 601–607PubMedGoogle Scholar
  5. 5.
    Bruce ME, Will RG, Ironside JW, McConnell I, Drummond D, Suttie A, McCardie L, Chree A, Hope J, Birkett C, Cousens S, Fraser H, Bostock CJ (1997) Transmissions to mice indicate that ‘new variant’ CJD is caused by the BSE agent. Nature 398: 489–501Google Scholar
  6. 6.
    Butler D (1996) Statistics suggest BSE now ‘Europa-wide’. Nature 382: 4PubMedCrossRefGoogle Scholar
  7. 7.
    Kimberlin RH, Walker CA (1982) Pathogenesis of mouse scrapie: patterns of agent replication in different parts of the CNS following intraperitoneal infection. J R Soc Med 75: 618–624PubMedGoogle Scholar
  8. 8.
    Kimberlin RH, Walker CA (1988) Incubation periods in six models of intraperitoneally injected scrapie depend mainly on the dynamics of agent replication within the nervous system and not the lymphoreticular system. J Gen Virol 69: 2953–2960PubMedCrossRefGoogle Scholar
  9. 9.
    Kimberlin RH, Walker CA (1989) Pathogenesis of scrapie in mice after intragastric infection. Virus Res 12: 213–220PubMedCrossRefGoogle Scholar
  10. 10.
    Kitamoto T, Shin R-W, Doh-ura K, Tomokane N, Miyazono M, Muramoto T, Tateishi J (1992) Abnormal isoform of prion proteins accumulates in the synaptic structures of the central nervous system in patients with Creutzfeldt-Jakob disease. Am J Pathol 140: 1285–1294PubMedGoogle Scholar
  11. 11.
    Korth C, Stierli B, Streit P, Moser M, Schaller O, Fischer R, Schulz-Schaeffer W, Kretzschmar H, Raeber A, Braun U, Ehrensperger F, Hornemann S, Glockshuber R, Riek R, Billeter M, Wüthrich K, Oesch B (1997) Prion (PrPSc)-specific epitope defined by a monoclonal antibody. Nature 390: 74–77PubMedCrossRefGoogle Scholar
  12. 12.
    Krasemann S, Groschup MH, Hanjieyer S, Hunsmann G, Bodemer W (1996) Generation of monoclonal antibodies against human prion proteins in PrP°/° mice. Mol Med 2: 725–734PubMedGoogle Scholar
  13. 13.
    Lasmézas CI, Deslys J-P, Demalmay R, Adjou KT, Lampury F, Dormont D, Robain O, Ironside J, Hauw J-J (1996) BSE transmission to macaques. Nature 381: 743–744PubMedCrossRefGoogle Scholar
  14. 14.
    Schaller O, Fatzer R, Stack M, Clark J, Cooley W, Biffiger K, Egli S, Doherr M, Vandevelde M, Heim D, Oesch B, Moser M (1999) Validation of a Western immunoblotting procedure for bovine PrPSc detection and its µse as a rapid surveillance method for the diagnosis of bovine spongiform encephalopathy (BSE). Acta Neuropathol 98: 437–443PubMedCrossRefGoogle Scholar
  15. 15.
    Schulz-SchaefferWJ, Tschöke S, KranefussN, DröseW, Hause-Reitner P, Giese A, Groschup MH, Kretzschmar HA (2000) The paraffin-embedded tissue blot detects PrP(Sc) early in the incubation time in prion diseases. Am J Pathol 156: 51–56CrossRefGoogle Scholar
  16. 16.
    Scott AC, Wells GAH, Stack MJ, White H, Dawson M (1990) Bovine spongiform encephalopathy: detection and quantitation of fibrils, fibril protein (PrP) and vacuolation in brain. Vet Microbiol 23: 295–304PubMedCrossRefGoogle Scholar
  17. 17.
    Scott MR, Will R, Ironside J, Nguyen HO, Trenmblay P, DeArmond SJ, Prusiner SB (1999) Compelling transgenetic evidence for transmission of bovine spongiform encephalopathy prions to humans. Proc Natl Acad Sei USA 96: 15137–15142CrossRefGoogle Scholar
  18. 18.
    Wells GAH, Scott AC, Johnson CT, Gunning RF, Hancock RD, Jeffrey M, Dawson M, Bradley R (1987) A novel progressive spongiform encephalopathy. VetRec 121:419–420PubMedCrossRefGoogle Scholar
  19. 19.
    Wells GAH, Spencer YI, Haritani M (1994) Configurations and topographic distribution of PrP in the central nervous system in bovine spongiform encephalopathy: an immunohistochemical study. Ann NY Acad Sci 724: 350–352PubMedCrossRefGoogle Scholar
  20. 20.
    Wells GAH, Wilesmith JW (1995) The neuropathology and epidemiology of bovine spongiform encephalopathy. Brain Pathol 5: 91–103PubMedCrossRefGoogle Scholar
  21. 21.
    Wells GAH, Wilesmith JW, McGill IS (1991) Bovine spongiform encephalopathy: a neuropathological perspective. Brain Pathol 1: 69–78PubMedCrossRefGoogle Scholar
  22. 22.
    Wilesmith JW, Wells GAH, Cranwell MP, Ryan JBM (1988) Bovine spongiform encephalopathy: epidemiologic studies. Vet Rec 123: 638–644PubMedGoogle Scholar
  23. 23.
    Will RQ, Ironside JW, Zeidler M, Cousens SN, 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 Wien 2000

Authors and Affiliations

  • W. J. Schulz-Schaeffer
    • 1
  • R. Fatzer
    • 2
  • M. Vandevelde
    • 2
  • H. A. Kretzschmar
    • 1
  1. 1.Institute of NeuropathologyGeorg-August UniversityGöttingenGermany
  2. 2.Institute of Animal NeurologyBernSwitzerland

Personalised recommendations