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Induction of epitopes associated with neurofibrillary tangles in clonal mouse neuroblastoma (S20Y) cells

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Summary

Accumulation of paired helical filaments (PHF) in neurofibrillary tangles is a key neuropathological hallmark in Alzheimer's disease (AD). To date, PHF have been found primarily in humans. Cultured murine cholinergic neuroblastoma (S20Y) cells, following exposure to a serum-free medium or a differentiation medium, developed immunoreactivity to anti-PHF antibodies, and to the Alz-50 by immunocytochemical and immunoblot analyses. Electron microscopic examination revealed abundant fascicles of 10-nm filaments coursing tortuously amongst organelles, such as mitochondria, endoplasmic reticulum and dense-core vesicles, in perikarya and in neuritic extensions. However, subcellular structures identical or similar to PHF could not be found in these non-human cells. This convenient cell culture model may prove to be useful for studying certain aspects of the mechanisms underlying the abnormal cytoskeletal alterations which are characteristic of AD and related neurodegenerative disorders.

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References

  1. Amano T, Richelson E, Nirenberg M (1972) Neurotransmitter synthesis by neuroblastoma clones. Proc Natl Acad Sci USA 69:258–263

    Google Scholar 

  2. Artlieb U, Krepler R, Wiche G (1985) Expression of microtubule-associates proteins, MAP-1 and MAP-2, in human neuroblastomas and differential diagnosis of immature neuroblasts. Lab Invest 53:684–691

    Google Scholar 

  3. Bancher C, Lassmann H, Budka H, Jellinger K, Grundke-Iqbal I, Iqbal K, Wiche G, Seitelberger F, Wisniewski HM (1989) An antigenic profile of Lewy bodies: immunocytochemical indication for protein phosphorylation and ubiquitination. J Neuropathol Exp Neurol 48:81–93

    Google Scholar 

  4. Bancher C, Brunner C, Lassmann H, Budka H, Jellinger K, Wiche G, Seitelberger F, Grundke-Iqbal I, Iqbal K, Wisniewski HM (1989) Accumulation of abnormally phosphorylated tau precedes the formation of neurofibrillary tangles in Alzheimer's disease. Brain Res 477:90–99

    Google Scholar 

  5. Blass JP, Baker AC, Sheu K-FR, Ko L, Black RS, Smith A (1989) Use of cultured skin fibroblasts in studies of Alzheimer's disease. In: Boller F, Katzman R, Rascol A, Signoret L, Christen Y (eds) Biological markers of Alzheimer's disease. Springer, Berlin Heidelberg New York, pp 153–162

    Google Scholar 

  6. Bottenstein JE (1983) Growth requirements of neural cells in vitro. Adv Cell Neurobiol 4:333–379

    Google Scholar 

  7. Conolly JA, Kalnins VI (1980) The distribution of tau and HMW microtubule-associated proteins in different cell types. Exp Cell Res 127:341–350

    Google Scholar 

  8. Cork LC, Powers RE, Selkoe DJ, Davies P, Geyer JJ, Price DL (1988) Neurofibrillary tangles and senile plaques in aged bears. J Neuropathol Exp Neurol 47:629–641

    Google Scholar 

  9. De Boni U, Crapper McLachlan DR (1985) Controlled induction of paired helical filaments of the Alzheimer type in cultured human neurons, by glutamate and aspartate. J Neurol Sci 68:105–118

    Google Scholar 

  10. Defossez A, Delacourte A (1987) Transformation of degenerating neurofibrils into amyloid substance in Alzheimer's disease: histochemical and immunohistochemical studies. J Neurol Sci 81:1–10

    Google Scholar 

  11. Galloway PG (1988) Antigenic characteristics of neurofibrillary tangles in progressive supranuclear palsy. Neurosci Lett 91:148–153

    Google Scholar 

  12. Galloway PG, Grundke-Iqbal I, Iqbal K, Perry G (1988) Lewy bodies contain epitopes both shared and distinct from Alzheimer neurofibrillary tangles. J Neuropathol Exp Neurol 47:654–663

    Google Scholar 

  13. Glenner GG, Eanes ED, Bladen HA, Linke RP, Termine JD (1974) β-Pleated sheet fibrils. A comparison of native amyloid with synthetic protein fibrils. J Histochem Cytochem 22:1141–1158

    Google Scholar 

  14. Goedert M, Wischik CM, Crowther RA, Walker JE, Klug A (1988) 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 USA 85:4051–4055

    Google Scholar 

  15. Grundke-Iqbal I, Iqbal K, Quinlan M, Tung Y-C, Zaidi MS, Wisniewski HM (1986)_Microtubule-associated protein tau. A component of Alzheimer paired helical fimalents. J Biol Chem 261:6084–6089

    Google Scholar 

  16. Hsu S-M, Raine L, Fanger H (1981) Use of avidin-biotinperoxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 29:577–580

    Google Scholar 

  17. Hyman BT, Van Hoesen GW, Wolozin BL, Davies P, Kromer LJ, Damasio AR (1988) Alz-50 antibody recognizes Alzheimer-related neuronal changes. An Neurol 23:371–379

    Google Scholar 

  18. Iqbal K, Grundke-Iqbal I, Smith AJ, Georgr L, Tung Y-C, Zaidi T (1989) Identification and localization of a τ peptide to paired helical filaments of Alzheimer disease. Proc Natl Acad Sci USA 86:5646–5650

    Google Scholar 

  19. Katzman R (1986) Alzheimer's disease. N Engl J Med 314:964–973

    Google Scholar 

  20. Kidd M (1963) Paired helical filaments in electron microscopy in Alzheimer's disease. Nature 197:192–193

    Google Scholar 

  21. Ko L, Koestner A, Wechsler W (1980) Morphological characterization of nitrosourea-induced glioma cell lines and clones. Acta Neuropathol 51:23–31

    Google Scholar 

  22. Ko L, Koestner A, Wechsler W (1980) Characterization of cell cycle and biological parameters of transplantable glioma cell lines and clones. Acta Neuropathol 51:107–111

    Google Scholar 

  23. Ko L, Sheu K-FR, Young O, Blass JP (1989) Expression of Alzheimer antigens in cultured mouse neuroblastoma cells. Trans Am Soc Neurochem 20:105 [A]

    Google Scholar 

  24. Ko L, Baker AC, Blass JP, Sheu K-FR (1990) Tissue culture models for the study of Alzheimer's disease. Neurobiol Aging 11:80 [A]

    Google Scholar 

  25. Ko L, Sheu K-FR, Young O, Thaler H, Blass JP (1990) Expression in cultured human neuroblastoma cells of epitopes associated with affected neurons in Alzheimer's disease. Am J Pathol 136:867–879

    Google Scholar 

  26. Kondo J, Honda T, Mori H, Hamada Y, Miura R, Ogawara M, Thara Y (1988) The carboxyl third of tau is tightly bound to paired helical filaments. Neuron 1:827–834

    Google Scholar 

  27. Kosik KS, Joachim CL, Selkoe DJ (1986) Microtubule-associated protein tau (τ) is a major antigenic component of paired helical filaments in Alzheimer disease. Proc Natl Acad Sci USA 83:4044–4048

    Google Scholar 

  28. Kosik KS, Orecchio LD, Binder L, Trojanowski JQ, Lee VMY, Lee G (1988) Epitopes that span the tau molecule are shared with paired helical filaments. Neuron 1:817–825

    Google Scholar 

  29. Ksiezak-Reding H, Davies P, Yen S-H (1988) Alz 50, a monoclonal antibody to Alzheimer's disease antigen, cross-reacts with tau proteins from bovine and normal human brain. J Biol Chem 263:7943–7947

    Google Scholar 

  30. Ksiezak-Reding H, Binder LI, Yen S-H (1988) Immunochemical and biochemical characterization of tau proteins in normal and Alzheimer's disease brains with Alz-50 and Tau 1. J Biol Chem 263:7948–7953

    Google Scholar 

  31. Langui D, Anderton BH, Brion JP, Ulrich J (1988) Effects of aluminium chloride on cultured cells from rat brain hemispheres. Brain Res 438:67–76

    Google Scholar 

  32. Love S, Saitoh T, Quijada S, Cole GM, Terry RD (1988) Alz-50, ubiquitin and tau immunoreactivity of neurofibrillary tangle, Pick bodies and Lewy bodies. J Neuropathol Exp Neurol 47:393–405

    Google Scholar 

  33. Love S, Burrola P, Terry RD, Wiley CA (1989) Immunoelectron microscopy of Alzheimer and Pick brain tissue labelled with the monoclonal antibody Alz-50. Neuropathol Appl Neurobiol 15:223–231

    Google Scholar 

  34. Masters CM, Multhaup G, Simms G, Pottgiesser J, Martins RN, Beyreuther K (1985) Neuronal origin of a cerebral amyloid: neurofibrillary tangles of Alzheimer's disease contain the same protein as the amyloid of plaque cores and blood vessels. EMBO J 4:2757–2763

    Google Scholar 

  35. Metuzals J, Robitaille Y, Houghton S, Gauthier S, Kang CY, Leblanc R (1988) Neuronal transformations in Alzheimer's disease. Cell Tissue Res 252:239–248

    Google Scholar 

  36. Nukina N, Kosik KS, Selkoe DJ (1988) The monoclonal antibody, Alz 50, recognizes tau proteins in Alzheimer's disease brain. Neurosci Lett 87:240–246

    Google Scholar 

  37. Papasozomenos SC (1989) Tau protein immunoreactivity in dementia of the Alzheimer type. II. Electron microscopy and pathogenetic implications. Effects of fixation on the morphology of the Alzheimer's abnormal filaments. Lab Invest 60:375–389

    Google Scholar 

  38. Pollock NJ, Binder LI, Mirra SS, Wood JG (1988) Alzheimer's disease: a model for study of cytoskeletal segregation as a determinant of neuronal form and function. In: Lasek RJ, Black MM, (eds) Intrinsic determinants of neuronal form and function. Alan R Liss, New York, pp 569–586

    Google Scholar 

  39. Probst A, Anderson BH, Ulrich J, Kohler R, Kahn J, Heitz PU (1983) Pick's disease: an immunocytochemical study of neuronal changes. Monoclonal antibodies show that Pick bodies share antigenic determinants with neurofibrillary tangles and neurofilaments. Acta Neuropathol 60:175–182

    Google Scholar 

  40. Roth M (1986) The association of clinical and neurological findings and its bearing on the classification and aetiology of Alzheimer's disease. Br Med Bull 42:42–50

    Google Scholar 

  41. Selkoe DJ (1987) Deciphering Alzheimer's disease: the pace quickens. Trends Neurosci 10:181–184

    Google Scholar 

  42. Selkoe DJ, Abraham CR (1986) Isolation of paired helical filaments and amyloid fibers from human brain. Methods Enzymol 134:388–404

    Google Scholar 

  43. Terry RD (1984) Alzheimer's disease. In: Scarpelli DG, Migaki G (eds) Comparative pathobiology of major age-related diseases: current status and research frontiers. Alan R. Liss, New York, pp 357–371

    Google Scholar 

  44. Terry RD, Katzman R (1983) Senile dementia of the Alzheimer type. Ann Neurol 14:497–506

    Google Scholar 

  45. Terry RD, Gonatas NK, Weiss M (1964) Ultrastructural studies in Alzheimer's disease presenile dementia. Am J Pathol 44:269–297

    Google Scholar 

  46. Towbin H, Staehelin T, Gordon J (1979) Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci USA 76:4350–4354

    Google Scholar 

  47. Weber K, Osborn M (1975) Proteins and sodium dodecyl sulfate: molecular weight determination on polyacrylamide gels and related procedures. In: Neurath H, Hill RL (eds) The Proteins, 3rd edn. Academic Press, New York, pp 179–223

    Google Scholar 

  48. Wischik CM, Novak M, Thogersen HC, Edwards PC, Runswick MJ, Jakes R, Walker JE, Milstein C, Roth M, Klug A (1988) Isolation of a fragment of tau derived from the core of the paired helical filament of Alzheimer disease. Proc Natl Acad Sci USA 85:4506–4510

    Google Scholar 

  49. Wolozin BL, Davies P (1987) Alzheimer-related neuronal protein A68: specificity and distribution. Ann Neurol 22:521–526

    Google Scholar 

  50. Wolozin BL, Pruchinicki A, Dickson DW, Davies P (1986) A neuronal antigen in the brains of Alzheimer patients. Science 232:648–650

    Google Scholar 

  51. Yamamoto T, Hirano A (1986) A comparative study of modified Bielschowsky, Bodian and thioflavin S stains on Alzheimer's neurofibrillary tangles. Neuropathol Appl Neurobiol 12:3–9

    Google Scholar 

  52. Yen S-H, Crowe A, Dickson DW (1985) Monoclonal antibodies to Alzheimer neurofibrillary tangles 1. Identification of polypeptides. Am J Pathol 120:282–291

    Google Scholar 

  53. Yen S-H, Dickson DW, Crowe A, Butler M, Shelanski ML (1986) Alzheimer's neurofibrillary tangles contain unique epitopes and epitopes in common with the heat-stable microtubule associated proteins tau and MAP2. Am J Pathol 126:81–91

    Google Scholar 

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Supported by grants from the Overbrook Foundation, the Will Rogers Institute, the Dr. I. Fund Foundation, the Winifred Masterson Burke Relief Foundation, the Alzheimer's Disease Research Program of the American Health Assistance Foundation and the National Institute of Aging (AG03853)

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Ko, L., Sheu, K.F.R., Young, O. et al. Induction of epitopes associated with neurofibrillary tangles in clonal mouse neuroblastoma (S20Y) cells. Acta Neuropathol 81, 30–40 (1990). https://doi.org/10.1007/BF00662635

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  • DOI: https://doi.org/10.1007/BF00662635

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