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. 1990 Apr;136(4):867–879.

Expression in cultured human neuroblastoma cells of epitopes associated with affected neurons in Alzheimer's disease.

L W Ko 1, K F Sheu 1, O Young 1, H Thaler 1, J P Blass 1
PMCID: PMC1877639  PMID: 1691594

Abstract

Of three human neuroblastoma lines tested, IMR32K (and IMR32 parental line) was the only cell line that, after its exposure to a differentiation medium, consistently developed materials recognized immunocytochemically by a panel of antibodies against paired helical filaments (PHF). Ultrastructurally, these cells accumulated, at their perikarya and neuritic extensions, spatially discrete arrays of fibrils, which occasionally occurred in twisted pairs. When these fibrillar structures appeared as paired helices, they exhibited dimensions and configurations reminiscent of PHF found in affected Alzheimer neurons, although less compact. Immunoelectron microscope examinations of the fibrillar structures in these neuroblastoma cells with one of these anti-PHF immunoprobes revealed that only subsets of fibrillar structures that appeared thickened or aggregated to form bundles were selectively immunolabeled. Cultures of these immortal neuroblastoma lines may provide a convenient model for studying aspects of PHF formation that are hard to examine in Alzheimer brain obtained at autopsy.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Artlieb U., Krepler R., Wiche G. Expression of microtubule-associated proteins, MAP-1 and MAP-2, in human neuroblastomas and differential diagnosis of immature neuroblasts. Lab Invest. 1985 Dec;53(6):684–691. [PubMed] [Google Scholar]
  2. Bancher C., Brunner C., Lassmann H., Budka H., Jellinger K., Wiche G., Seitelberger F., Grundke-Iqbal I., Iqbal K., Wisniewski H. M. Accumulation of abnormally phosphorylated tau precedes the formation of neurofibrillary tangles in Alzheimer's disease. Brain Res. 1989 Jan 16;477(1-2):90–99. doi: 10.1016/0006-8993(89)91396-6. [DOI] [PubMed] [Google Scholar]
  3. Biedler J. L., Helson L., Spengler B. A. Morphology and growth, tumorigenicity, and cytogenetics of human neuroblastoma cells in continuous culture. Cancer Res. 1973 Nov;33(11):2643–2652. [PubMed] [Google Scholar]
  4. Birrell G. B., Hedberg K. K., Griffith O. H. Pitfalls of immunogold labeling: analysis by light microscopy, transmission electron microscopy, and photoelectron microscopy. J Histochem Cytochem. 1987 Aug;35(8):843–853. doi: 10.1177/35.8.2439584. [DOI] [PubMed] [Google Scholar]
  5. Brion J. P., Flament-Durand J., Dustin P. Alzheimer's disease and tau proteins. Lancet. 1986 Nov 8;2(8515):1098–1098. doi: 10.1016/s0140-6736(86)90495-2. [DOI] [PubMed] [Google Scholar]
  6. Connolly J. A., Kalnins V. I. The distribution of tau and HMW microtubule-associated proteins in different cell types. Exp Cell Res. 1980 Jun;127(2):341–350. doi: 10.1016/0014-4827(80)90439-5. [DOI] [PubMed] [Google Scholar]
  7. Davies P., Wolozin B. L. Recent advances in the neurochemistry of Alzheimer's disease. J Clin Psychiatry. 1987 May;48 (Suppl):23–30. [PubMed] [Google Scholar]
  8. De Boni U., McLachlan D. R. Controlled induction of paired helical filaments of the Alzheimer type in cultured human neurons, by glutamate and aspartate. J Neurol Sci. 1985 May;68(2-3):105–118. doi: 10.1016/0022-510x(85)90093-0. [DOI] [PubMed] [Google Scholar]
  9. Défossez A., Delacourte A. Transformation of degenerating neurofibrils into amyloid substance in Alzheimer's disease: histochemical and immunohistochemical studies. J Neurol Sci. 1987 Oct;81(1):1–10. doi: 10.1016/0022-510x(87)90179-1. [DOI] [PubMed] [Google Scholar]
  10. Emory C. R., Ala T. A., Frey W. H., 2nd Ganglioside monoclonal antibody (A2B5) labels Alzheimer's neurofibrillary tangles. Neurology. 1987 May;37(5):768–772. doi: 10.1212/wnl.37.5.768. [DOI] [PubMed] [Google Scholar]
  11. Galloway P. G., Grundke-Iqbal I., Iqbal K., Perry G. Lewy bodies contain epitopes both shared and distinct from Alzheimer neurofibrillary tangles. J Neuropathol Exp Neurol. 1988 Nov;47(6):654–663. doi: 10.1097/00005072-198811000-00008. [DOI] [PubMed] [Google Scholar]
  12. Goedert M., Wischik C. M., Crowther R. A., Walker J. E., Klug A. Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease: identification as the microtubule-associated protein tau. Proc Natl Acad Sci U S A. 1988 Jun;85(11):4051–4055. doi: 10.1073/pnas.85.11.4051. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Grundke-Iqbal I., Iqbal K., Quinlan M., Tung Y. C., Zaidi M. S., Wisniewski H. M. Microtubule-associated protein tau. A component of Alzheimer paired helical filaments. J Biol Chem. 1986 May 5;261(13):6084–6089. [PubMed] [Google Scholar]
  14. Grundke-Iqbal I., Iqbal K., Tung Y. C., Quinlan M., Wisniewski H. M., Binder L. I. Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci U S A. 1986 Jul;83(13):4913–4917. doi: 10.1073/pnas.83.13.4913. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Grundke-Iqbal I., Iqbal K., Tung Y. C., Wisniewski H. M. Alzheimer paired helical filaments: immunochemical identification of polypeptides. Acta Neuropathol. 1984;62(4):259–267. doi: 10.1007/BF00687607. [DOI] [PubMed] [Google Scholar]
  16. Hirokawa N., Shiomura Y., Okabe S. Tau proteins: the molecular structure and mode of binding on microtubules. J Cell Biol. 1988 Oct;107(4):1449–1459. doi: 10.1083/jcb.107.4.1449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hsu S. M., Raine L., Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981 Apr;29(4):577–580. doi: 10.1177/29.4.6166661. [DOI] [PubMed] [Google Scholar]
  18. Hyman B. T., Van Hoesen G. W., Wolozin B. L., Davies P., Kromer L. J., Damasio A. R. Alz-50 antibody recognizes Alzheimer-related neuronal changes. Ann Neurol. 1988 Apr;23(4):371–379. doi: 10.1002/ana.410230410. [DOI] [PubMed] [Google Scholar]
  19. Ihara Y., Abraham C., Selkoe D. J. Antibodies to paired helical filaments in Alzheimer's disease do not recognize normal brain proteins. Nature. 1983 Aug 25;304(5928):727–730. doi: 10.1038/304727a0. [DOI] [PubMed] [Google Scholar]
  20. KIDD M. Paired helical filaments in electron microscopy of Alzheimer's disease. Nature. 1963 Jan 12;197:192–193. doi: 10.1038/197192b0. [DOI] [PubMed] [Google Scholar]
  21. Katzman R. Alzheimer's disease. N Engl J Med. 1986 Apr 10;314(15):964–973. doi: 10.1056/NEJM198604103141506. [DOI] [PubMed] [Google Scholar]
  22. Ko L., Koestner A., Wechsler W. Morphological characterization of nitrosourea-induced glioma cell lines and clones. Acta Neuropathol. 1980;51(1):23–31. doi: 10.1007/BF00688846. [DOI] [PubMed] [Google Scholar]
  23. Kondo J., Honda T., Mori H., Hamada Y., Miura R., Ogawara M., Ihara Y. The carboxyl third of tau is tightly bound to paired helical filaments. Neuron. 1988 Nov;1(9):827–834. doi: 10.1016/0896-6273(88)90130-4. [DOI] [PubMed] [Google Scholar]
  24. Kosik K. S., Joachim C. L., Selkoe D. J. Microtubule-associated protein tau (tau) is a major antigenic component of paired helical filaments in Alzheimer disease. Proc Natl Acad Sci U S A. 1986 Jun;83(11):4044–4048. doi: 10.1073/pnas.83.11.4044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Kosik K. S., Orecchio L. D., Binder L., Trojanowski J. Q., Lee V. M., Lee G. Epitopes that span the tau molecule are shared with paired helical filaments. Neuron. 1988 Nov;1(9):817–825. doi: 10.1016/0896-6273(88)90129-8. [DOI] [PubMed] [Google Scholar]
  26. Ksiezak-Reding H., Davies P., Yen S. H. Alz 50, a monoclonal antibody to Alzheimer's disease antigen, cross-reacts with tau proteins from bovine and normal human brain. J Biol Chem. 1988 Jun 15;263(17):7943–7947. [PubMed] [Google Scholar]
  27. Langui D., Anderton B. H., Brion J. P., Ulrich J. Effects of aluminium chloride on cultured cells from rat brain hemispheres. Brain Res. 1988 Jan 12;438(1-2):67–76. doi: 10.1016/0006-8993(88)91324-8. [DOI] [PubMed] [Google Scholar]
  28. Mori H., Kondo J., Ihara Y. Ubiquitin is a component of paired helical filaments in Alzheimer's disease. Science. 1987 Mar 27;235(4796):1641–1644. doi: 10.1126/science.3029875. [DOI] [PubMed] [Google Scholar]
  29. Nukina N., Ihara Y. One of the antigenic determinants of paired helical filaments is related to tau protein. J Biochem. 1986 May;99(5):1541–1544. doi: 10.1093/oxfordjournals.jbchem.a135625. [DOI] [PubMed] [Google Scholar]
  30. Nukina N., Kosik K. S., Selkoe D. J. The monoclonal antibody, Alz 50, recognizes tau proteins in Alzheimer's disease brain. Neurosci Lett. 1988 May 3;87(3):240–246. doi: 10.1016/0304-3940(88)90455-7. [DOI] [PubMed] [Google Scholar]
  31. Rasool C. G., Abraham C., Anderton B. H., Haugh M., Kahn J., Selkoe D. J. Alzheimer's disease: immunoreactivity of neurofibrillary tangles with anti-neurofilament and anti-paired helical filament antibodies. Brain Res. 1984 Sep 24;310(2):249–260. doi: 10.1016/0006-8993(84)90148-3. [DOI] [PubMed] [Google Scholar]
  32. Riekkinen P. J., Laulumaa V., Sirviö J., Soininen H., Helkala E. L. Recent progress in the research of Alzheimer's disease. Med Biol. 1987;65(2-3):83–88. [PubMed] [Google Scholar]
  33. Schliwa M., van Blerkom J. Structural interaction of cytoskeletal components. J Cell Biol. 1981 Jul;90(1):222–235. doi: 10.1083/jcb.90.1.222. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Selkoe D. J., Abraham C. R. Isolation of paired helical filaments and amyloid fibers from human brain. Methods Enzymol. 1986;134:388–404. doi: 10.1016/0076-6879(86)34105-3. [DOI] [PubMed] [Google Scholar]
  35. Sternberger N. H., Sternberger L. A., Ulrich J. Aberrant neurofilament phosphorylation in Alzheimer disease. Proc Natl Acad Sci U S A. 1985 Jun;82(12):4274–4276. doi: 10.1073/pnas.82.12.4274. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. TERRY R. D., GONATAS N. K., WEISS M. ULTRASTRUCTURAL STUDIES IN ALZHEIMER'S PRESENILE DEMENTIA. Am J Pathol. 1964 Feb;44:269–297. [PMC free article] [PubMed] [Google Scholar]
  37. Terry R. D., Katzman R. Senile dementia of the Alzheimer type. Ann Neurol. 1983 Nov;14(5):497–506. doi: 10.1002/ana.410140502. [DOI] [PubMed] [Google Scholar]
  38. Wischik C. M., Novak M., Edwards P. C., Klug A., Tichelaar W., Crowther R. A. Structural characterization of the core of the paired helical filament of Alzheimer disease. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4884–4888. doi: 10.1073/pnas.85.13.4884. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Wischik C. M., Novak M., Thøgersen H. C., Edwards P. C., Runswick M. J., Jakes R., Walker J. E., Milstein C., Roth M., Klug A. Isolation of a fragment of tau derived from the core of the paired helical filament of Alzheimer disease. Proc Natl Acad Sci U S A. 1988 Jun;85(12):4506–4510. doi: 10.1073/pnas.85.12.4506. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Wisniewski H. M., Soifer D. Neurofibrillary pathology: current status and research perspectives. Mech Ageing Dev. 1979 Jan;9(1-2):119–142. doi: 10.1016/0047-6374(79)90125-8. [DOI] [PubMed] [Google Scholar]
  41. Wolozin B. L., Pruchnicki A., Dickson D. W., Davies P. A neuronal antigen in the brains of Alzheimer patients. Science. 1986 May 2;232(4750):648–650. doi: 10.1126/science.3083509. [DOI] [PubMed] [Google Scholar]
  42. Wood J. G., Mirra S. S., Pollock N. J., Binder L. I. Neurofibrillary tangles of Alzheimer disease share antigenic determinants with the axonal microtubule-associated protein tau (tau) Proc Natl Acad Sci U S A. 1986 Jun;83(11):4040–4043. doi: 10.1073/pnas.83.11.4040. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Yamamoto T., Hirano A. A comparative study of modified Bielschowsky, Bodian and thioflavin S stains on Alzheimer's neurofibrillary tangles. Neuropathol Appl Neurobiol. 1986 Jan-Feb;12(1):3–9. doi: 10.1111/j.1365-2990.1986.tb00677.x. [DOI] [PubMed] [Google Scholar]
  44. Yen S. H., Crowe A., Dickson D. W. Monoclonal antibodies to Alzheimer neurofibrillary tangles. 1. Identification of polypeptides. Am J Pathol. 1985 Aug;120(2):282–291. [PMC free article] [PubMed] [Google Scholar]
  45. Yen S. H., Dickson D. W., Crowe A., Butler M., Shelanski M. L. Alzheimer's neurofibrillary tangles contain unique epitopes and epitopes in common with the heat-stable microtubule associated proteins tau and MAP2. Am J Pathol. 1987 Jan;126(1):81–91. [PMC free article] [PubMed] [Google Scholar]

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