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Electron Microscopy of Prion Diseases

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Prion Diseases

Part of the book series: Neuromethods ((NM,volume 129))

Abstract

Electron microscopy provided detailed description of submicroscopic changes in prion diseases or transmissible spongiform encephalopathies (TSEs). For Creutzfeldt-Jakob disease (CJD and its variant, vCJD) and fatal familial insomnia (FFI) only vacuolation (spongiform change) and the presence of tubulovesicular structures are consistent findings. Other changes—i.e., the presence of “myelinated” vacuoles, branching cisterns, neuroaxonal dystrophy, and autophagic vacuoles—were present in different proportions in either CJD or FFI, but they are nonspecific ultrastructural findings that can also occur in other neurodegenerative conditions.

The hallmark of Gerstmann-Sträussler-Scheinker disease (GSS) and vCJD is the amyloid plaque, but plaques of GSS and kuru are different than those of vCJD. Whereas the former are typical unicentric “kuru-type” or multicentric plaques, the latter are unicentric “florid” plaques. Also, kuru plaques are non-neuritic, whereas GSS florid plaques are usually neuritic; however, a proportion of plaques from GSS were also found to have non-neuritic characteristics. Thus, the presence or absence of dystrophic neurites is not a discriminatory factor for GSS and vCJD. Furthermore, plaques from GSS with different mutations were also slightly different. In GSS with mutation P102L, 232T and A117V plaques were “stellate” while in one case with 144 base pair insertion and in GSS-A117V, “round” plaques were also observed, and typical “primitive” “neuritic” plaques, i.e., composed of dystrophic neurites with little or no amyloid, were found only in a P102L case from the original Austrian family. In two cases of sporadic CJD, the kuru “stellate” plaque predominated.

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References

  1. Merz PA, Somerville RA, Wisniewski HM, Iqbal J (1981) Abnormal fibrils from scrapie-infected brain. Acta Neuropathol (Berl) 60:63–74

    Article  Google Scholar 

  2. Merz PA, Rohwer RG, Kascak R et al (1984) Infection specific particle from the unconventional slow virus diseases. Science 225(4660):437–440

    Article  CAS  PubMed  Google Scholar 

  3. McKinley MP, Bolton DC, Prusiner SB (1983) A protease resistant protein is a structural component of the scrapie prion. Cell 35(1):57–62

    Article  CAS  PubMed  Google Scholar 

  4. Dealler S, Rainov NG (2003) Pentosan polysulfate as a prophylactic and therapeutic agent against prion disease. IDrugs 6(5):470–478. Erratum in: IDrugs (2004) 7:88

    CAS  PubMed  Google Scholar 

  5. Brown P, Cathala F, Raubertas RF et al (1987) The epidemiology of Creutzfeldt-Jakob disease: conclusion of a 15-year investigation in France and review of the world literature. Neurology 37(6):895–895

    Article  CAS  PubMed  Google Scholar 

  6. Liberski PP, Streichenberger N, Giraud P et al (2005) Ultrastructural pathology of prion diseases revisited: brain biopsy studies. Neuropathol Appl Neurobiol 31(1):88–96

    Article  CAS  PubMed  Google Scholar 

  7. Liberski PP, Sikorska B, Hauw JJ et al (2008) Tubulovesicular structures are a consistent (and unexplained) finding in the brains of humans with prion diseases. Virus Res 132(1-2):226–228

    Article  CAS  PubMed  Google Scholar 

  8. Liberski PP, Budka H, Sluga E et al (1992) Tubulovesicular structures in Creutzfeldt-Jakob disease. Acta Neuropathol (Berl) 84:238–243

    Article  CAS  Google Scholar 

  9. Streichenberger N, Jordan D, Verejan I et al (2000) The first case of new variant Creutzfeldt-Jakob disease in France: clinical data and neuropathological findings. Acta Neuropathol (Berl) 99(6):704–708

    Article  CAS  Google Scholar 

  10. Sikorska B, Liberski PP, Sobow T et al (2009) Ultrastructural study of florid plaques in variant Creutzfeldt-Jakob disease: a comparison with amyloid plaques in kuru, sporadic Creutzfeldt-Jakob disease and Gerstmann-Sträussler-Scheinker disease. Neuropathol Appl Neurobiol 35(1):46–59

    Article  CAS  PubMed  Google Scholar 

  11. Hainfellner J, Brantner-Inhaler S, Cervenakova L et al (1995) The original Gerstmann-Sträussler-Scheinker family of Austria: divergent clinicopathological phenotypes but constant PrP genotype. Brain Pathol 5(3):201–211

    Article  CAS  PubMed  Google Scholar 

  12. Liberski PP, Budka H (1995) Ultrastructural pathology of Gerstmann-Sträussler-Scheinker disease. Ultrastruct Pathol 19(1):23–36

    Article  CAS  PubMed  Google Scholar 

  13. Boellaard JW, Schlote W (1980) Subakute spongiforme Encephalopathie mit multiformer Plaquebildung. Eigenartige familiar-hereditare Kranknheit des Zentralnervensystems [spino-cerebellare Atrophie mit Demenz, Plaques and plaqueahnlichen im Klein- and Grosshirn (Gerstmann, Sträussler, Scheinker)]. Acta Neuropathol (Berl) 49:205–212

    Article  CAS  Google Scholar 

  14. Schlote W, Boellaard JW, Schumm F, Stohr M (1980) Gerstmann-Sträussler-Scheinker's disease. Electron microscopic observations on a brain biopsy. Acta Neuropathol (Berl) 52(3):203–211

    Article  CAS  Google Scholar 

  15. Schumm F, Boellaard JW, Schlote W, Stohr M (1981) Morbus Gerstmann-Sträussler-Scheinker. Familie SCh.—Ein Bericht uber drei Kranke. Arch Psychiatr Nervenkr 230(3):179–196

    Article  CAS  PubMed  Google Scholar 

  16. Brown P, Goldfarb LG, Brown WT et al (1991) Clinical and molecular genetic study of a large German kindred with Gerstmann-Sträussler-Scheinker syndrome. Neurology 41(3):375–375

    Article  CAS  PubMed  Google Scholar 

  17. Liberski PP, Barcikowska M, Cervenakova L et al (1998) A case of sporadic Creutzfeldt-Jakob disease with a Gerstmann-Sträussler-Scheinker phenotype but no alterations in the PRNP gene. Acta Neuropathol 96(4):425–430

    Article  CAS  PubMed  Google Scholar 

  18. Liberski PP, Bratosiewicz J, Barcikowska M et al (2000) A case of sporadic Creutzfeldt-Jakob disease with a Gerstmann-Sträussler-Scheinker phenotype but no alterations in the PRNP gene. Acta Neuropathol 100(2):233–234

    Article  CAS  PubMed  Google Scholar 

  19. Gelpi E, Kovacs GG, Ströbel T et al (2005) Prion disease with a 144 base pair insertion: unusual cerebellar prion protein immunoreactivity. Acta Neuropathol 110(5):513–519

    Article  CAS  PubMed  Google Scholar 

  20. Kopp N, Richard M, Giraud P et al (2001) Un cas d’insomnie fatale. Rev Neurol (Paris) 157:332–333

    Google Scholar 

  21. Kopp N, Richard M, Liberski PP, Laplanche J, Giraud P, Biacabe A, Streichenberger N, Mallie F, Gross E, Boulliat J, Perret-Liaudet A (2000) A case of fatal familial insomnia: neuropathology and biochemistry. Abstract no C34-05. In: Abstracts of the XVth International Congress of Neuropathology, Birmingham, September 3–6th, 2000. Brain Pathol 10:671

    Google Scholar 

  22. Simmons MM, Blamire IW, Austin AR (1996) Simple method for the perfusion-fixation of adult bovine brain. Res Vet Sci 60(3):247–250

    Article  CAS  PubMed  Google Scholar 

  23. Liberski PP, Brown P (2007) Disease-sepcific particles without prion protein in prion diseases—phenomenon or epiphenomenon? Neuropathol Appl Neurobiol 33(4):395–397

    Article  CAS  PubMed  Google Scholar 

  24. Jellinger K (1973) Neuroaxonal dystrophy. Its natural history and related disorders. In: Zimmerman HM (ed) Progress in neuropathology, vol 2. Grune & Stratton, New York, pp 129–180

    Google Scholar 

  25. Liberski PP, Yanagihara R, Gibbs CJ Jr, Gajdusek DC (1989) Scrapie as a model for neuroaxonal dystrophy: ultrastructural studies. Exp Neurol 106(2):133–141

    Article  CAS  PubMed  Google Scholar 

  26. Sikorska B, Liberski PP, Brown P (2008) Subependymal plaques in scrapie-affected hamster brains—why are they so different from compact kuru plaques? Folia Neuropathol 46(1):32–42

    PubMed  Google Scholar 

  27. DeArmond SJ, McKinley MP, Barry RA et al (1985) Identification of prion amyloid filaments in scrapie-infected brain. Cell 41(1):221–235

    Article  CAS  PubMed  Google Scholar 

  28. Sigurdson CJ, Manco G, Schwarz P et al (2006) Strain fidelity of chronic wasting disease upon murine adaptation. J Virol 80(24):12303–12311

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Falsig J, Aguzzi A (2008) The prion organotypic slice culture assay—POSCA. Nat Protoc 3(4):555–562

    Article  CAS  PubMed  Google Scholar 

  30. Falsig J, Sonati T, Herrmann US et al (2012) Prion pathogenesis is faithfully reproduced in cerebellar organotypic slice cultures. PLoS Pathog 8(11):e1002985

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Sonati T, Reimann RR, Falsig J et al (2013) The toxicity of antiprion antibodies is mediated by the flexible tail of the prion protein. Nature 501(7465):102–106

    Article  CAS  PubMed  Google Scholar 

  32. Kovacs GG, Kalev O, Budka H (2004) Contribution of neuropathology to the understanding of human prion disease. Folia Neuropathol 42(Suppl A):69–76

    PubMed  Google Scholar 

  33. Liberski PP, Yanagihara R, Gajdusek DC (1993) The spongiform vacuole—the hallmark of slow virus diseases. In: Liberski PP (ed) Light and electron microscopic neuropathology of slow virus disorders. CRC Press, Boca Raton, pp 155–180

    Google Scholar 

  34. Armstrong RA, Cairns NJ, Ironside JW, Lantos PL (2002) The spatial patterns of prion protein deposits in cases of variant Creutzfeldt-Jakob disease. Acta Neuropathol (Berl) 104:665–669

    CAS  Google Scholar 

  35. Armstrong RA, Cairns NJ, Lantos PL (2001) Quantification of the vacuolation (spongiform change) and prion protein deposition in 11 patients with sporadic Creutzfeldt-Jakob disease. Acta Neuropathol (Berl) 102(6):591–596

    Article  CAS  Google Scholar 

  36. Zlotnik I (1957) Significance of vacuolated neurones in the medulla of sheep affected with scrapie. Nature 180(4582):393–394

    Article  CAS  PubMed  Google Scholar 

  37. Beck E, Bak IJ, Christ JF et al (1975) Experimental kuru in the spider monkey. Histopathological and ultrastructural studies of the brain during early stages of incubation. Brain 98(4):595–612

    Article  CAS  PubMed  Google Scholar 

  38. Beck E, Daniel PM, Davey AJ et al (1982) The pathogenesis of transmissible spongiform encephalopathy: an ultrastructural study. Brain 105(4):755–786

    Article  PubMed  Google Scholar 

  39. Liberski PP, Yanagihara R, Asher DM et al (1990) Reevaluation of the ultrastructural pathology of experimental Creutzfeldt-Jakob disease. Brain 113(1):121–137

    Article  PubMed  Google Scholar 

  40. Liberski PP, Yanagihara R, Wells GAH et al (1992) Ultrastructural pathology of axons and myelin in experimental scrapie in hamsters and bovine spongiform encephalopathy in cattle and a comparison with the panencephalopathic type of Creutzfeldt-Jakob disease. J Comp Pathol 106(4):383–398

    Article  CAS  PubMed  Google Scholar 

  41. Jeffrey M, Scott JR, Williams A, Fraser H (1992) Ultrastructural features of spongiform encephalopathy transmitted to mice from three species of bovidae. Acta Neuropathol (Berl) 84(5):559–569

    Article  CAS  Google Scholar 

  42. Kim JH, Manuelidis EE (1986) Serial ultrastructural study of experimental Creutzfeldt-Jacob disease in guinea pigs. Acta Neuropathol 69(1-2):81–90

    Article  CAS  PubMed  Google Scholar 

  43. Liberski PP, Brown DR, Sikorska B (2008) Cell death and autophagy in prion diseases (transmissible spongiform encephalopathies). Folia Neuropathol 46(1):1–25

    CAS  PubMed  Google Scholar 

  44. Liberski PP, Sikorska B, Bratosiewicz-Wasik J et al (2004) Neuronal cell death in transmissible spongiform encephalopathies (prion diseases) revisited: from apoptosis to autophagy. Int J Biochem Cell Biol 36(12):2473–2490

    Article  CAS  PubMed  Google Scholar 

  45. David-Ferreira JF, David-Ferreira KL, Gibbs CJ Jr, Morris JA (1968) Scrapie in mice: ultrastructural observations in the cerebral cortex. Proc Soc Exp Biol Med 127(1):313–320

    Article  CAS  PubMed  Google Scholar 

  46. Gibson PH, Doughty LA (1989) An electron microscopic study of inclusion bodies in synaptic terminals of scrapie-infected animals. Acta Neuropathol (Berl) 77(4):420–425

    Article  CAS  Google Scholar 

  47. Liberski PP, Asher DM, Yanagihara R et al (1989) Serial ultrastructural studies of scrapie in hamsters. J Comp Pathol 101(4):429–442

    Article  CAS  PubMed  Google Scholar 

  48. Liberski PP, Budka H (1994) Tubulovesicular structures in Gerstmann-Sträussler-Scheinker disease. Acta Neuropathol (Berl) 88(5):491–492

    Article  CAS  Google Scholar 

  49. Liberski PP, Jeffrey M, Goodsir C (1997) Tubulovesicular structures are not labeled using antibodies to prion protein (PrP) with the immunogold electron microscopy techniques. Acta Neuropathol (Berl) 93(3):260–264

    Article  CAS  Google Scholar 

  50. Siakotos AN, Raveed D, Longa G (1979) The discovery of a particle unique to brain and spleen subcellular fractions from scrapie-infected mice. J Gen Virol 43(2):417–422

    Article  CAS  PubMed  Google Scholar 

  51. Liberski PP, Yanagihara R, Gibbs CJ Jr, Gajdusek DC (1990) Appearance of tubulovesicular structures in experimental Creutzfeldt-Jakob disease and scrapie precedes the onset of clinical disease. Acta Neuropathol (Berl) 79(4):349–354

    Article  CAS  Google Scholar 

  52. Jeffrey M, Goodsir CM, Race RE, Chesebro R (2004) Scrapie-specific neuronal lesions are independent of neuronal PrP expression. Ann Neurol 55(6):781–792

    Article  CAS  PubMed  Google Scholar 

  53. Manuelidis L, Yu ZX, Barquero N, Mullins B (2007) Cells infected with scrapie and Creutzfeldt-Jakob disease agents produce intracellular 25-nm virus-like particles. Proc Natl Acad Sci U S A 104(6):1965–1970. Erratum in: Proc Natl Acad Sci USA (2007) 104:6090

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Correspondence to Paweł P. Liberski .

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Liberski, P.P. (2017). Electron Microscopy of Prion Diseases. In: Liberski, P. (eds) Prion Diseases. Neuromethods, vol 129. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7211-1_7

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  • DOI: https://doi.org/10.1007/978-1-4939-7211-1_7

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7209-8

  • Online ISBN: 978-1-4939-7211-1

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