Skip to main content
SpringerLink
Log in

Prion Diseases and Dementia

  • Chapter
Molecular Mechanisms of Dementia

Part of the book series: Contemporary Neuroscience ((CNEURO))

Abstract

Prion diseases are a group of neurodegenerative conditions of humans and animals that include sporadic, inherited, and transmitted forms. They are best characterized by their distinctive pathogenic mechanism, which is shared by all three forms. The central event in the pathogenesis of these diseases is thought to be a change in protein conformation that results in the conversion of a normal protein, identified as cellular prion protein (PrPC), into an isoform that is partially resistant to proteases (PrPres) (1). The molecular events leading to this conformational change, however, remain largely unknown.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Prusiner, S. B. and DeArmond, S. J. (1994) Prion diseases and neurodegeneration, Ann. Rev. Neurosci. 17, 311–319.

    Article  PubMed  CAS  Google Scholar 

  2. Parchi, P. and Gambetti, P. (1995) Human prion diseases, Curr. Opinion Neurol. 8, 286–293.

    Article  CAS  Google Scholar 

  3. Fraser, H. and Dickinson, A. G. (1973) Scrapie in mice. Agent-strain differences in the distribution and intensity of grey matter vacuolation, J. Comp. Pathol. 83, 23–40.

    Article  Google Scholar 

  4. Hecker, R., Taraboulos, A., Scott, M., Pan, K. M., Yang, S. L., Torchia, M., Jendroska, K., DeArmond, S. J., and Prusiner, S. B. (1992) Replication of distinct scrapie prion isolates is region specific in brains of transgenic mice and hamsters, Genes Dey. 6, 1213–1228.

    Article  CAS  Google Scholar 

  5. Brown, P., Gibbs, C. J., Rodgers-Johnson, P., Asher, D. M., Sulima, M. P., Bacote, A., Goldfarb, L. G., and Gajdusek, D. C. (1994) Human spongiform encephalopathy: The National Institutes of Health series of 300 cases of experimentally transmitted disease, Ann. Neurol. 35, 513–529.

    Article  PubMed  CAS  Google Scholar 

  6. Parchi, P., Castellani, R., Capellari, S., Ghetti, B., Young, K., Chen, S. G., Farlow, M., Dickson, D. W., Sima, A. A. F., Trojanowski, J. Q., Petersen, R. B., and Gambetti, R (1996) Molecular basis of phenotypic variability in sporadic Creutzfelt-Jakob disease, Ann. Neurol. 39, 767–778.

    Article  PubMed  CAS  Google Scholar 

  7. Richardson, E. P. and Masters, C. L. (1995) The nosology of Creutzfeldt-Jakob disease and conditions related to the accumulation of PrPcm in the nervous system, Brain Pathol. 5, 33–41.

    Article  PubMed  Google Scholar 

  8. Brown, P., Goldfarb, L. G., Kovanen, J., Haltia, M., Cathala, F., Sulima, M., Gibbs, C. J., and Gajdusek, D. C. (1992) Phenotypic characteristics of familial Creutzfeldt-Jakob disease associated with the codon 178 Asn PRNP mutation, Ann. Neurol. 31, 282–285.

    Article  PubMed  CAS  Google Scholar 

  9. Bertoni, J. M., Brown, P., Goldfarb, L. G., Rubenstein, R., and Gajdusek, D. C. (1992) Familial Creutzfeldt-Jakob disease (codon 200 mutation) with supranuclear palsy, JAMA 268, 2413–2415.

    Article  PubMed  CAS  Google Scholar 

  10. Tietjen, G. E. and Drury, I. (1990) Familial Creutzfeldt-Jakob disease without periodic EEG activity, Ann. Neurol. 28, 585–588.

    Article  PubMed  CAS  Google Scholar 

  11. Pocchiari, M., Salvatore, M., Cutruzzola, F., Genuardi, M., Allocatelli, C. T., Masullo, C., Macchi, G., Alema, G., Galgani, S., Xi, Y. G., Petraroli, R., Silvestrini, M. C., and Brunori, M. (1993) A new point mutation of the prion protein gene in Creutzfeldt-Jakob disease, Ann. Neurol. 34, 802–807.

    Article  PubMed  CAS  Google Scholar 

  12. Kitamoto, T. and Tateishi, J. (1994) Human prion diseases with variant prion protein, Phil. Trans. R. Soc. Lond. B. 343, 391–398.

    Article  CAS  Google Scholar 

  13. Goldfarb, L. G., Petersen, R. B., Tabaton, M., Brown, P., LeBlanc, A. C., Montagna, P., Cortelli, P., Julien, J., Vital, C., Pendlebury, W. W., Haltia, M., Willis, P. R., Hauw, J. J., McKeever, P. E., Monari, L., Schrank, B., Swergold, G. D., Autilio-Gambetti, L., Gajdusek, C., Lugaresi, E., and Gambetti, P. (1992) Fatal familial insomnia and Familial Creutzfeldt Jakob disease: disease phenotype determined by a DNA polymorphism, Science 258, 806–808.

    Article  PubMed  CAS  Google Scholar 

  14. Parchi, P., Castellani, R., Cortelli, P., Montagna, P., Chen, S. G., Petersen, R. B., Manetto, V., Vnencak-Jones, C. L., McLean, M. J., Sheller, J. R., Lugaresi, E., Autilio-Gambetti, L., and Gambetti, P. (1995) Regional distribution of protease-resistant prion protein in Fatal Familial Insomnia, Ann Neurol. 38, 21–29.

    Article  PubMed  CAS  Google Scholar 

  15. Perani, D., Cortelli, P., Lucignani, G., Montagna, P., Tinuper, R, Gallassi, R., Gambetti, R, Lenzi, G. L., Lugaresi, E., and Fazio, F. (1993) [18F] FDG PET in Fatal familial insomnia: the functional effects of thalamic lesions, Neurology 43, 2565–2569.

    Google Scholar 

  16. Perani, D., Parchi, P., Cortelli, P., Montagna, P., Grassi, F., Castellani, R., Gambetti, P., Lugaresi, E., and Fazio, F. (1995) Relationship between protease-resistant prion protein distribution and in vivo regional cerebral metabolism in Fatal Familial Insomnia (FFI), Neurology 45, A406.

    Article  Google Scholar 

  17. Gallassi, R., Morreale, A., Gambetti, P., and Lugaresi, E. (1992) Fatal familial insomnia: neuropsychological study of a disease with thalamic degeneration, Cortex 28, 175–187.

    PubMed  CAS  Google Scholar 

  18. Gallassi, R., Morreale, A., Montagna, P., Cortelli, P., Avoni, P., Castellani, R., Gambetti, P., and Lugaresi, L. (1996) Fatal familial insomnia: behavioral and cognitive features, Neurology 46, 935–939.

    Article  PubMed  CAS  Google Scholar 

  19. Lugaresi, E., Medori, R., Montagna, P., Baruzzi, A., Cortelli, P., Lugaresi, A., Tinuper, R, Zucconi, M., and Gambetti, R (1986) Fatal familial insomnia and dysautonomia with selective degeneration of thalamic nuclei, N. Engl. J. Med. 315, 997–1003.

    Article  PubMed  CAS  Google Scholar 

  20. Montagna, R, Cortelli, P., Tinuper, P., Sforza, E., Avoni, R, Gallassi, R., Morreale, A., Roiter, I., Perani, D., Lucignani, G., Fazio, F., and Lugaresi, E. (1994) Fatal familial insomnia: A disease that emphasizes the role of the thalamus in the regulation of sleep and vegetative functions, in Fatal Familial Insomnia: Inherited Prion Diseases, Sleep, and the Thalamus ( Guilleminault, C., Lugaresi, E., Montagna, P., and Gambetti, P., eds.), Raven, New York, pp. 1–14.

    Google Scholar 

  21. Tinuper, P., Montagna, P., Medori, R., Cortelli, P., Zucconi, M., Baruzzi, A., and Lugaresi, E. (1989) The thalamus participates in the regulation of the sleep-waking cycle. A clinicopathological study in Fatal Familial Thalamic degeneration, Electroencephalogic Clin. Neurophysiol. 73, 117–120.

    Article  CAS  Google Scholar 

  22. Ghetti, B., Dlouhy, S. R., Giaccone, G., Bugiani, O., Frangione, B., Farlow, M. R., and Tagliavini, F. (1995) Gerstmann-Sträussler-Scheinker disease and the Indiana kindred, Brain Pathol. 5, 61–75.

    Article  PubMed  CAS  Google Scholar 

  23. Ghetti, B., Piccardo, P., Spillantini, M. G., Ichimiya, Y., Porro, M., Perini, F., Kitamoto, T., Tateishi, J., Seiler, C., Frangione, B., Bugiani, O., Giaconne, G., Prelli, F., Goedert, M., Dlouhy, S. R., and Tagliavini, F. (1996) Vascular variant of prion protein cerebral amyloidosis with i-positive neurofibrillary tangles: The phenotype of the stop codon 145 mutation in PRNP, Proc. Natl. Acad. Sci. USA 93, 744–748.

    Article  PubMed  CAS  Google Scholar 

  24. Dlouhy, S. R., Hsiao, K., Farlow, M. R., Foroud, T., Conneally, P. M., Johnson, P., Prusiner, S. B., Hooles, M. E., and Ghetti, B. (1992) Linkage of the Indiana kindred of GerstmannSträussler-Scheinker disease to the prion protein gene, Nature Genet. 1, 64–67.

    Article  PubMed  CAS  Google Scholar 

  25. a. Unverzagt, F. W., Farlow, M. R., Norton, J., Dlouhy, S. R., Young, K., and Ghetti, B. Neurophysiological function in patients with Gerstmann-Sträussler-Scheinker disease from the Indiana Kindred (F198S), in press.

    Google Scholar 

  26. Bolton, D. C., McKinley, M. P., and Prusiner, S. B. (1982) Identification of a protein that purifies with the scrapie protein, Science 218, 1309, 1310.

    Google Scholar 

  27. Kascsak, R. J., Rubenstein, R., Merz, P. A., Carp, R. I., Robakis, N. K., Wisniewski, H. M., and Diringer, H. (1986) Immunological comparison of scrapie-associated fibrils isolated from animals infected with four different scrapie strains, J. Virol. 59, 676–683.

    Google Scholar 

  28. Rubenstein, R., Merz, P. A., Kascsak, R. J., Carp, R. I., Scalici, C. L., Fama, C. L., and Wisniewski, H. M. (1987) Detection of scrapie-associated fibrils (SAF) and SAF proteins from scrapie-affected sheep, J. Infect. Dis. 156, 36–42.

    Article  PubMed  CAS  Google Scholar 

  29. Hope, J., Ritchie, L., Farquhar, C., Somerville, R., and Hunter, N. (1989) Bovine spongifonn encephalopathy: a scrapie-like disease of British cattle, Prog. Clin. Biol. Res. 317, 659–667.

    PubMed  CAS  Google Scholar 

  30. Brown, P., Coker-Vann, M., Pomeroy, K., Franko, M., Asher, D. M., Gibbs, C. J., and Gajdusek, D. C. (1986) Diagnosis of Creutzfeldt-Jakob disease by western blot identification of marker protein in human brain tissue, N. Engl. J. Med. 314, 547–551.

    Article  PubMed  CAS  Google Scholar 

  31. Bockman, J. M., Kingsbury, D. R., McKinley, M. P., Bendheim, P. E., and Prusiner, S. B. (1985) Creutzfeldt-Jakob disease prion proteins in human brains, N. Engl. J Med. 312, 73–78.

    Article  PubMed  CAS  Google Scholar 

  32. Bessen, R. A. and Marsh, R. F. (1994) Distinct PrP properties suggest the molecular basis of strain variation in transmissible mink encephalopathy, J. Virol. 68, 7859–7868.

    PubMed  CAS  Google Scholar 

  33. Monari, L., Chen, S. C., Brown, P., Parchi, P., Petersen, R. B., Mikol, J., Gray, F., Cortelli, P., Montagna, P., Ghetti, B., Goldfarb, L. G., Gajdusek, D. C., Lugaresi, E., Gambetti, P., and Autilio-Gambetti, L. (1994) Fatal Familial Insomnia and Familial Creutzfeldt-Jakob disease: Different prion proteins determined by a DNA polymorphism, Proc. Natl. Acad. Sci. USA, 91, 2839–2842.

    Article  PubMed  CAS  Google Scholar 

  34. Tagliavini, F., Prelli, F., Ghiso, J., Bugiani, O., Serban, D., Prusiner, S. B., Farlow, M. R., Ghetti, B., and Frangione, B. (1991) Amyloid protein of Gertsmann-Straussler-Scheinker disease (Indiana kindred) is an l lkd fragment of prion protein with an N-terminal glycine at codon 58, EMBO J. 10, 513–519.

    PubMed  CAS  Google Scholar 

  35. Brandner, S., Isenmann, S., Raeber, A., Fischer, M., Sailer, A., Kobayashi, Y., Marino, S., Weissmann, C., and Aguzzi, A. (1996) Normal host prion protein necessary for scrapieinduced neurotoxicity, Nature 379, 339–343.

    Article  PubMed  CAS  Google Scholar 

  36. Collinge, J., Whittington, M. A., Sidle, K. C., Smith, C. J., Palmer, M. S., Clarke, A. R., and Jefferys, J. G. R. (1994) Prion protein is necessary for normal synaptic function, Nature 370, 295–297.

    Article  PubMed  CAS  Google Scholar 

  37. Jendroska, K., Heinzel, F. P., Torchia, M., Stowring, L., Kretzschmar, H. A., Kon, A., Stern, A., Prusiner, S. B., and DeArmond, S. J. (1991) Proteinase-resistant prion protein accumulation in Syrian hamster brain correlations with regional pathology and scrapie infectivity, Neurology 41, 1482–1490.

    Article  PubMed  CAS  Google Scholar 

  38. Castellani, R., Parchi, P., Stahl, J., Capellari, S., Cohen, M., and Gambetti, P. (1996) Early pathological and biochemical changes in Creutzfeldt-Jakob disease: study of brain biopsies, Neurology 46, 1690–1693.

    Article  PubMed  CAS  Google Scholar 

  39. Kitamoto, T., Shin, R. W., Doh-ura, K., Tomokane, N., Miyazono, M., Muramoto, T., and Tateishi, J. (1992) Abnormal isoform of prion proteins accumulates in the synaptic struc-tures of the central nervous system in patients with Creutzfeldt-Jakob disease, Am. J. Pathol. 140, 1285–1294.

    PubMed  CAS  Google Scholar 

  40. Jeffrey, M., Goodsir, C. M., Bruce, M., McBride, P. A., Scott, J. R., and Halliday, W. G. (1994) Correlative light and electron microscopy studies of PrP localization in 87V scrapie, Brain Res. 656, 329–343.

    Article  PubMed  CAS  Google Scholar 

  41. Clinton, J., Forsyth, C., Royston, M. C., and Roberts, G. W. (1993) Synaptic degeneration is the primary neuropathological feature in prion disease: a preliminary study, NeuroReport 4, 65–68.

    Article  PubMed  CAS  Google Scholar 

  42. Forloni, G., Angeretti, N., Chiesa, R., Monzani, E., Salmona, M., Bugiani, O., and Tagliavini, F. (1993) Neurotoxicity of a prion protein fragment, Nature 362, 543–546.

    Article  PubMed  CAS  Google Scholar 

  43. Brown, D. R., Herms, J., and Kretzschmar, H. A. (1994) Mouse cortical cells lacking cellular PrP survive in culture with a neurotoxic PrP fragment, NeuroReport 5, 2057–2060.

    Article  PubMed  CAS  Google Scholar 

  44. Shyng, S. L., Huber, M. T., and Harris, D. A. (1993) A prion protein cycles between the cell surface and an endocytic compartment in cultured neuroblastoma cells, J. Biol. Chem. 268, 15,922–15, 928.

    Google Scholar 

  45. Chen, S. G., Teplow, D. B., Parchi, P., Teller, J. K., Gambetti, P., and Autilio-Gambetti, L. (1995) Truncated forms of the human prion protein in normal brain and in prion diseases, J. Biol. Chem. 270, 19,173–19, 180.

    Google Scholar 

  46. Ghetti, B., Piccardo, P., Frangione, B., Bugiani, O., Giaccone, G., Young, K., Prelli, F., Farlow, M. R., Dloughy, S. R., and Tagliavini, F. (1996) Prion protein amyloidosis, Brain Pathol. 6, 127–145.

    Article  PubMed  CAS  Google Scholar 

  47. Piccardo, P., Ghetti, B., Dickson, D. W., Vinters, H. V., Giaccone, G., Bugiani, O., Tagliavini, F., Young, K., Phil, D., Dloughy, S. R., Seiler, C., Jones, C. K., Lazzarini, A., Golbe, L. I., Zimmerman, T. R., Perlman, S. L., McLachlan, D. C., St. George-Hyslop, P. H., and Lennox, A. (1995) Gertsmann-Straussler-Scheinker disease (PRNP P102L): Amyloid deposits are best recognized by antibodies directed to epitopes in PrP region 90–165, J. Neurol. Exp. Neurol. 54, 790–801.

    Article  CAS  Google Scholar 

  48. Hainfellner, J. A., Brantner-Inthaler, S., Cervenakova, L., Brown, P., Kitamoto, T., Tateishi, J., Diringer, H., Liberski, P. P., Regele, H., Feucht, M., Mayr, N., Wessely, P., Summer, K., Seitelberger, F., and Budka, H. (1995) The original Gertsmann-Sträussler-Scheinker family ofAustria: Divergent clinicopathological phenotypes but constant PrP genotype, Brain Pathol. 5, 201–211.

    Article  PubMed  CAS  Google Scholar 

  49. Tagliavini, F., Prelli, F., Verga, L., Giaccone, G., Sarma, R., Gorevic, P., Ghetti, B., Passerini, F., Ghibaudi, E., Forloni, G., Salmona, M., Bugiani, O., and Frangione, B. (1993) Synthetic peptides homologous to prion protein residues 106–147 form amyloid-like fibrils in vitro, Proc. Natl. Acad. Sci. USA 90, 9678–9682.

    Article  PubMed  CAS  Google Scholar 

  50. Castano, E. M. and Frangione, B. (1995) Non-Alzheimer’s disease amyloidoses of the nervous system, Curr. Opinion Neurol. 8, 279–285.

    Article  CAS  Google Scholar 

  51. Petersen, R. B., Parchi, P., Richardson, S. L., Urig, C. B., and Gambetti, P. (1996) Effect of the DI78N mutation and the codon 129 polymorphism on the metabolism of the prion protein, J. Biol. Chem. 271,21, 12,661–12, 668.

    Google Scholar 

  52. Caughey, B. and Raymond, G. J. (1991) The scrapie-associated form of PrP is made from a cell surface precursor that is both protease-and phospholipase-sensitive, J. Biol. Chem. 266, 18,217–18, 223.

    Google Scholar 

  53. Chen, S. G., Parchi, P., Brown, P., Roos, R. P., Vnencak-Jones, C. L., and Gambetti, P. (1996) Fatal familial insomnia and familial Creutzfeldt-Jakob disease: abnormal prion protein (PrPres) encoded by the mutant allele, J. Neuropath. Exp. Neurol. 55,5, Al24.

    Google Scholar 

  54. Collinge, J., Whittington, M. A., Sidle, K. C. L., Smith, C. J., Palmer, M. S., Clarke, A. R., and Jeffreys, J. G. R. (1994) Prion protein is necessary for normal synaptic function, Nature 370, 295–297.

    Article  PubMed  CAS  Google Scholar 

  55. Tobler, I., Gaus, S. E., Deboer, T., Achermann, P., Fischer, M., Rülicke, T., Moser, M., Oesch, B., McBride, P. A., and Manson, J. C. (1996) Altered circadian activity rhythms and sleep in mice devoid of prion protein, Nature 380, 639–642.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. Piero Parchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pierluigi Gambetti
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Genetics and Aging Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA

    Wilma Wasco  & Rudolph E. Tanzi  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1997 Springer Science+Business Media New York

About this chapter

Cite this chapter

Parchi, P., Gambetti, P. (1997). Prion Diseases and Dementia. In: Wasco, W., Tanzi, R.E. (eds) Molecular Mechanisms of Dementia. Contemporary Neuroscience. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-471-9_18

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-471-9_18

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4757-5889-4

  • Online ISBN: 978-1-59259-471-9

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation