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Neuropathology, Immunohistochemistry, and Biochemistry in Human Prion Diseases

  • Diane L. RitchieEmail author
  • James W. Ironside
Protocol
  • 388 Downloads
Part of the Neuromethods book series (NM, volume 129)

Abstract

Human prion diseases are rare fatal neurodegenerative conditions that occur as sporadic, inherited, and acquired disorders. All are defined by characteristic neuropathological changes and by the accumulation of a disease-associated form of the prion protein in the brain. In variant CJD, prion protein also accumulates in lymphoid tissues and in the peripheral nervous system. Examination of the brain in human prion diseases is essential for a definite diagnosis and for disease surveillance.

In this chapter we bring over 20 years’ experience of research and diagnosis in human prion diseases to provide detailed information on how to handle brain tissue from a case of human prion disease safely in a laboratory. We also describe how to make the diagnosis of a human prion disease using histological and biochemical techniques for the detection of disease-associated prion protein in the brain, and provide helpful notes for practical guidance and troubleshooting in the laboratory.

Key words

Neuropathology Brain CJD prion protein Immunohistochemistry Western blot PET blot 

References

  1. 1.
    Prusiner SB (1982) Novel proteinaceous infectious particles cause scrapie. Science 216(4542):136–144PubMedCrossRefGoogle Scholar
  2. 2.
    Gambetti P, Kong Q, Zou W et al (2003) Sporadic and familial CJD: classification and characterisation. Br Med Bull 66(1):213–239PubMedCrossRefGoogle Scholar
  3. 3.
    Prusiner SB, DeArmond SJ (1994) Prion diseases and neurodegeneration. Annu Rev Neurosci 17(1):311–339PubMedCrossRefGoogle Scholar
  4. 4.
    Will RG, Ironside JW, Zeidler M et al (1996) A new variant of Creutzfeldt-Jakob disease in the UK. Lancet 347(9006):921–925PubMedCrossRefGoogle Scholar
  5. 5.
    Peden AH, Ironside JW, Head MW (2013) Risk of transmission of Creutzfeldt-Jakob disease by blood transfusion. In: Zou WQ, Gambetti P (eds) Prions and diseases. Springer, New YorkGoogle Scholar
  6. 6.
    National CJD Research & Surveillance Unit (1990–2015) Monthly surveillance figures. http://www.cjd.ed.ac.uk/documents/figs.pdf. Accessed 21 Sept 2015
  7. 7.
    Gill ON, Spencer Y, Richard-Loendt A et al (2013) Prevalent abnormal prion protein in human appendixes after bovine spongiform encephalopathy epizootic: large scale survey. Br Med J 347:f5675CrossRefGoogle Scholar
  8. 8.
    Taylor DM (2000) Inactivation of transmissible degenerative encephalopathy agents. A review. Vet J 159(1):10–17PubMedCrossRefGoogle Scholar
  9. 9.
    Taylor DM (2003) Preventing accidental transmission of human transmissible spongiform encephalopathy. Br Med Bull 66(1):293–303PubMedCrossRefGoogle Scholar
  10. 10.
    Advisory committee on Dangerous Pathogens (2013) Guidance: Minimise Transmission Risks of CJD and vCJD in Healthcare settings. http://www.gov.uk/government/publications/guidance-from-the-acdp-tse-risk-management-subgroup-formerly-tse-working-group. Accessed 21 Sept 2015
  11. 11.
    World Health Organization (2003) Infection control guidelines for transmissible spongiform encephalopathies. http://who.int/csr/resources/publications/bse/WHO_CDS_APH_2000_3/en/. Accessed 21 Sept 2015
  12. 12.
    Head MW, Ironside JW, Ghetti B et al (2015) Prion diseases. In: Love S, Budka H, Ironside JW, Perry A (eds) Greenfields neuropathology, 9th edn. CRC Press/Taylor & Francis Group, Boca RatonGoogle Scholar
  13. 13.
    Suvarna KS, Layton C, Bancroft JD (2013) The hematoxylins and eosin. In: Suvarna KS, Layton C, Bancroft JD (eds) Bancroft’s theory and practice of histological techniques, 7th edn. Churchill Livingston/Elsevier, LondonGoogle Scholar
  14. 14.
    Ironside JW, Ritchie DL, Head MW (2005) Phenotypic variability in human prion diseases. Neuropathol Appl Neurobiol 21:565–579CrossRefGoogle Scholar
  15. 15.
    Bell JE, Gentleman SM, Ironside JW et al (1997) Prion protein immunocytochemistry-UK five centre consensus report. Neuropathol Appl Neurobiol 23(1):26–35PubMedCrossRefGoogle Scholar
  16. 16.
    Kovacs G, Head MW, Hegyi I et al (2002) Immunohistochemistry for the prion protein: a comparison of different monoclonal antibodies in human prion disease subtypes. Brain Pathol 12(1):1–11PubMedCrossRefGoogle Scholar
  17. 17.
    Kitamoto T, Shin RW, Doh-ura K et al (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(6):1285–1294PubMedPubMedCentralGoogle Scholar
  18. 18.
    Liberski PP, Yanagihara R, Brown P et al (1996) Microwave treatment enhances the immunostaining of amyloid deposits in both the transmissible and non-transmissible amyloidoses. Neurodegeneration 5(1):95–99PubMedCrossRefGoogle Scholar
  19. 19.
    Kitamoto T, Ogomori K, Tateishi J et al (1987) Formic acid pretreatments enhances immunostaining of cerebral and systemic amyloids. Lab Investig 57(2):230–236PubMedGoogle Scholar
  20. 20.
    Hilton DA, Ghani AC, Conyers L et al (2004) Prevalance of lymphoreticular prion protein accumulation in UK tissue samples. J Pathol 203(3):733–739PubMedCrossRefGoogle Scholar
  21. 21.
    Ritchie DL, Head MW, Ironside JW (2004) Advances in the detection of prion protein in peripheral tissues of variant Creutzfelt-Jakob disease patients using paraffin-embedded tissue blotting. Neuropathol Appl Neurobiol 30(4):360–368PubMedCrossRefGoogle Scholar
  22. 22.
    Jarrett JT, Landsbury PT Jr (1993) Seeding “one dimensional crystallization” of amyloid: a pathogenic mechanism in Alzheimers disease and scrapie? Cell 73(6):1055–1058PubMedCrossRefGoogle Scholar
  23. 23.
    Prusiner SB, Scott MR, DeArmond SJ (1998) Prion protein biology. Cell 93(3):337–348PubMedCrossRefGoogle Scholar
  24. 24.
    Parchi P, Castellani R, Capellari S et al (1996) Molecular basis of phenotypic variability in sporadic Creutzfeldt-Jakob disease. Ann Neurol 39(6):767–778PubMedCrossRefGoogle Scholar
  25. 25.
    Collinge J, Sidle KCL, Meads J et al (1996) Molecular analysis of prion strain variation and the aetiology of “new variant” CJD. Nature 383(6602):685–690PubMedCrossRefGoogle Scholar
  26. 26.
    Head MW, Bunn TJ, Bishop MT et al (2004) Prion protein heterogeneity in sporadic but not variant Creutzfeldt-Jakob disease UK cases 1991–2002. Ann Neurol 55(6):851–859PubMedCrossRefGoogle Scholar
  27. 27.
    Parchi S, Capellari S, Chen SG et al (1997) Typing prion isoforms. Nature 386(6622):232–233PubMedCrossRefGoogle Scholar
  28. 28.
    Bruce ME, McConnell I, Will RG et al (2001) Detection of variant Creutzfeldt-Jakob disease infectivity in extraneural tissues. Lancet 358(9277):208–209PubMedCrossRefGoogle Scholar
  29. 29.
    Wadsworth JD, Joiner S, Hill AF et al (2001) Tissue distribution of protease resistant prion protein in variant Creutzfeldt-Jakob disease using a highly sensitive immunoblotting assay. Lancet 358(9277):171–180PubMedCrossRefGoogle Scholar
  30. 30.
    Safar J, Geschwind MD, Deering C et al (2005) Diagnosis of human prion diseases. Proc Natl Acad Sci U S A 102(9):3501–3506PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Orru CD, Caughey B (2011) Prion seeded conversion and amplification assays. Top Curr Chem 305:121–133PubMedCrossRefGoogle Scholar
  32. 32.
    Saborio GP, Permanne B, Soto C (2001) Sensitive detection of pathological prion protein by cyclic amplification of protein misfolding. Nature 411(6839):810–813PubMedCrossRefGoogle Scholar
  33. 33.
    Atarashi R, Moore A, Sim VL et al (2007) Ultrasensitive detection of scrapie prion protein using seeded conversion of recombinant prion protein. Nat Methods 4(8):645–650PubMedCrossRefGoogle Scholar
  34. 34.
    McGuire LI, Peden AH, Orru CD et al (2012) Real time quaking-induced conversion analysis of cerebrospinal fluid in sporadic Creutzfelt-Jakob disease. Ann Neurol 72(2):278–285PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Suvarna KS, Layton C, Bancroft JD (2013) Amyloid. In: Suvarna KS, Layton C, Bancroft JD (eds) Bancroft’s theory and practice of histological techniques, 7th edn. Churchill Livingston/Elsevier, LondonGoogle Scholar
  36. 36.
    Head MW, Yull HM, Ritchie DL et al (2013) Variably protease-sensitivity prionopathy in the UK: a retrospective review 1991–2008. Brain 136(4):1102–1115PubMedCrossRefGoogle Scholar
  37. 37.
    Kovacs GG, Zerbi P, Voigtlander T et al (2002) The prion protein in human neurodegenerative diseases. Neurosci Lett 329(3):269–272PubMedCrossRefGoogle Scholar
  38. 38.
    McLennan NF, Brennan PM, McNeil A et al (2004) Prion protein accumulation in hypoxic brain damage. Am J Pathol 165(1):227–235PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Parchi P, Giese A, Capellari S et al (1998) Different patterns of truncated prion protein fragments correlate with distinct phenotypes in P102L Gerstmann-Sträusler-Scheinker disease. Proc Natl Acad Sci U S A 95(14):8322–8327PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media LLC 2017

Authors and Affiliations

  1. 1.National CJD Research & Surveillance UnitCentre for Clinical Brain Sciences, School of Clinical Sciences, University of Edinburgh, Western General HospitalEdinburghUK

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