• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of amjpatholAmerican Journal of Pathology For AuthorsAmerican Journal of Pathology SubscribeAmerican Journal of Pathology SearchAmerican Journal of Pathology Current IssueAmerican Journal of Pathology About the JournalAmerican Journal of Pathology
Am J Pathol. Jun 1992; 140(6): 1285–1294.
PMCID: PMC1886543

Abnormal isoform of prion proteins accumulates in the synaptic structures of the central nervous system in patients with Creutzfeldt-Jakob disease.


A new method, which enabled the first immunohistochemical documentation of abnormal prion protein (PrP) in all patients with Creutzfeldt-Jakob disease (CJD), was established. This method designated as "hydrolytic autoclaving" revealed punctate PrPCJD stainings around the neuronal cell bodies and dendrites in CJD brains. These punctate stainings were almost identical with that of synaptophysin, suggesting PrPCJD accumulations in the synaptic structures. Subcellular fractionation revealed that prion protein in Creutzfeldt-Jakob disease (PrPCJD) was most concentrated in the synaptosomal fraction. In CJD patients with a long clinical course, synaptophysin immunoreactivity decreased, and synaptic PrPCJD accumulated with a wider distribution. These results suggest that synaptic PrPCJD accumulations might be responsible for the neuronal dysfunction and degeneration in CJD.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (3.5M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Prusiner SB. Novel proteinaceous infectious particles cause scrapie. Science. 1982 Apr 9;216(4542):136–144. [PubMed]
  • Kitamoto T, Ogomori K, Tateishi J, Prusiner SB. Formic acid pretreatment enhances immunostaining of cerebral and systemic amyloids. Lab Invest. 1987 Aug;57(2):230–236. [PubMed]
  • Kitamoto T, Tateishi J. Immunohistochemical confirmation of Creutzfeldt-Jakob disease with a long clinical course with amyloid plaque core antibodies. Am J Pathol. 1988 Jun;131(3):435–443. [PMC free article] [PubMed]
  • Bockman JM, Kingsbury DT, McKinley MP, Bendheim PE, Prusiner SB. Creutzfeldt-Jakob disease prion proteins in human brains. N Engl J Med. 1985 Jan 10;312(2):73–78. [PubMed]
  • Brown P, Coker-Vann M, Pomeroy K, Franko M, Asher DM, Gibbs CJ, Jr, Gajdusek DC. Diagnosis of Creutzfeldt-Jakob disease by Western blot identification of marker protein in human brain tissue. N Engl J Med. 1986 Feb 27;314(9):547–551. [PubMed]
  • Oesch B, Westaway D, Wälchli M, McKinley MP, Kent SB, Aebersold R, Barry RA, Tempst P, Teplow DB, Hood LE, et al. A cellular gene encodes scrapie PrP 27-30 protein. Cell. 1985 Apr;40(4):735–746. [PubMed]
  • Basler K, Oesch B, Scott M, Westaway D, Wälchli M, Groth DF, McKinley MP, Prusiner SB, Weissmann C. Scrapie and cellular PrP isoforms are encoded by the same chromosomal gene. Cell. 1986 Aug 1;46(3):417–428. [PubMed]
  • Kitamoto T, Yi R, Mohri S, Tateishi J. Cerebral amyloid in mice with Creutzfeldt-Jakob disease is influenced by the strain of the infectious agent. Brain Res. 1990 Jan 29;508(1):165–167. [PubMed]
  • Bruce ME, McBride PA, Farquhar CF. Precise targeting of the pathology of the sialoglycoprotein, PrP, and vacuolar degeneration in mouse scrapie. Neurosci Lett. 1989 Jul 17;102(1):1–6. [PubMed]
  • Piccardo P, Safar J, Ceroni M, Gajdusek DC, Gibbs CJ., Jr Immunohistochemical localization of prion protein in spongiform encephalopathies and normal brain tissue. Neurology. 1990 Mar;40(3 Pt 1):518–522. [PubMed]
  • Serban D, Taraboulos A, DeArmond SJ, Prusiner SB. Rapid detection of Creutzfeldt-Jakob disease and scrapie prion proteins. Neurology. 1990 Jan;40(1):110–117. [PubMed]
  • Taraboulos A, Serban D, Prusiner SB. Scrapie prion proteins accumulate in the cytoplasm of persistently infected cultured cells. J Cell Biol. 1990 Jun;110(6):2117–2132. [PMC free article] [PubMed]
  • Doi-Yi R, Kitamoto T, Tateishi J. Immunoreactivity of cerebral amyloidosis is enhanced by protein denaturation treatments. Acta Neuropathol. 1991;82(4):260–265. [PubMed]
  • Weidemann A, König G, Bunke D, Fischer P, Salbaum JM, Masters CL, Beyreuther K. Identification, biogenesis, and localization of precursors of Alzheimer's disease A4 amyloid protein. Cell. 1989 Apr 7;57(1):115–126. [PubMed]
  • Doh-ura K, Tateishi J, Sasaki H, Kitamoto T, Sakaki Y. Pro----leu change at position 102 of prion protein is the most common but not the sole mutation related to Gerstmann-Sträussler syndrome. Biochem Biophys Res Commun. 1989 Sep 15;163(2):974–979. [PubMed]
  • Kitamoto T, Muramoto T, Hilbich C, Beyreuther K, Tateishi J. N-terminal sequence of prion protein is also integrated into kuru plaques in patients with Gerstmann-Sträussler syndrome. Brain Res. 1991 Apr 5;545(1-2):319–321. [PubMed]
  • Shin RW, Iwaki T, Kitamoto T, Tateishi J. Hydrated autoclave pretreatment enhances tau immunoreactivity in formalin-fixed normal and Alzheimer's disease brain tissues. Lab Invest. 1991 May;64(5):693–702. [PubMed]
  • Huttner WB, Schiebler W, Greengard P, De Camilli P. Synapsin I (protein I), a nerve terminal-specific phosphoprotein. III. Its association with synaptic vesicles studied in a highly purified synaptic vesicle preparation. J Cell Biol. 1983 May;96(5):1374–1388. [PMC free article] [PubMed]
  • Kitamoto T, Mohri S, Tateishi J. Organ distribution of proteinase-resistant prion protein in humans and mice with Creutzfeldt-Jakob disease. J Gen Virol. 1989 Dec;70(Pt 12):3371–3379. [PubMed]
  • Kitamoto T, Hikita K, Tashima T, Tateishi J, Sato Y. Scrapie-associated fibrils (SAF) purification method yields amyloid proteins from systemic and cerebral amyloidosis. Biosci Rep. 1986 May;6(5):459–465. [PubMed]
  • Kitamoto T, Muramoto T, Mohri S, Doh-Ura K, Tateishi J. Abnormal isoform of prion protein accumulates in follicular dendritic cells in mice with Creutzfeldt-Jakob disease. J Virol. 1991 Nov;65(11):6292–6295. [PMC free article] [PubMed]
  • Haber SN, Nauta WJ. Ramifications of the globus pallidus in the rat as indicated by patterns of immunohistochemistry. Neuroscience. 1983 Jun;9(2):245–260. [PubMed]
  • Goto S, Hirano A. Synaptophysin expression in the striatum in Huntington's disease. Acta Neuropathol. 1990;80(1):88–91. [PubMed]
  • Meyer RK, McKinley MP, Bowman KA, Braunfeld MB, Barry RA, Prusiner SB. Separation and properties of cellular and scrapie prion proteins. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2310–2314. [PMC free article] [PubMed]
  • Safar J, Ceroni M, Piccardo P, Liberski PP, Miyazaki M, Gajdusek DC, Gibbs CJ., Jr Subcellular distribution and physicochemical properties of scrapie-associated precursor protein and relationship with scrapie agent. Neurology. 1990 Mar;40(3 Pt 1):503–508. [PubMed]
  • Pras M, Schubert M, Zucker-Franklin D, Rimon A, Franklin EC. The characterization of soluble amyloid prepared in water. J Clin Invest. 1968 Apr;47(4):924–933. [PMC free article] [PubMed]
  • Kascsak RJ, Rubenstein R, Merz PA, Tonna-DeMasi M, Fersko R, Carp RI, Wisniewski HM, Diringer H. Mouse polyclonal and monoclonal antibody to scrapie-associated fibril proteins. J Virol. 1987 Dec;61(12):3688–3693. [PMC free article] [PubMed]
  • Ahern TJ, Klibanov AM. The mechanisms of irreversible enzyme inactivation at 100C. Science. 1985 Jun 14;228(4705):1280–1284. [PubMed]
  • Fraser H. Neuronal spread of scrapie agent and targeting of lesions within the retino-tectal pathway. Nature. 1982 Jan 14;295(5845):149–150. [PubMed]
  • Fraser H, Dickinson AG. Targeting of scrapie lesions and spread of agent via the retino-tectal projection. Brain Res. 1985 Oct 28;346(1):32–41. [PubMed]
  • Liberski PP, Yanagihara R, Gibbs CJ, Jr, Gajdusek DC. Spread of Creutzfeldt-Jakob disease virus along visual pathways after intraocular inoculation. Arch Virol. 1990;111(1-2):141–147. [PubMed]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...