Acta Neuropathologica

, Volume 48, Issue 2, pp 105–112 | Cite as

Presence of neurofilament protein in Alzheimer's neurofibrillary tangles (ANT)

An immunofluorescent study
  • Tsuyoshi Ishii
  • Seiichi Haga
  • Satoshi Tokutake
Original Works

Summary

Localization of neurofilament (NF) protein in the neurons of rat's brain, spinal cord, and peripheral nerves was studied by the indirect immunofluorescent method using goat-antirabbit plus rabbit anti-NF antibody. The NF protein was purified from the calf brain by the method of Yen et al. (1976). Control sections were treated with nonspecific rabbit serum and with the experimental rabbit serum absorbed with the NF protein. Fluorescence in the axons of the neurons, such as the motor neurons of the spinal cord, peripheral nerves, pontine nuclei, or those of the cerebellar cortex including Purkinje cells, was strong, while that of the dendrites and perikarya was weaker. Glial processes also showed intense fluorescence. Fluorescence in glia cells was interpreted as representing an insufficient separation of NF protein as the antigen from the glial fibrillary acidic protein (GFA). Localization of NF protein in the Alzheimer's neurofibrillary tangles (ANT) in the hippocampus of the brain of a patient with Alzheimer's disease, was examined by the same way as described above. ANT showed the whole gamut of the color of fluorescence from completely positive green to mixed green with increasingly bluer tints. Astroglial processes also showed intense green fluorescence. The results suggest that ANT comprises NF protein as the structural component and that the increasingly blue fluorescence may represent fewer antigenic sites due to increasing degrees of structural insolubilization or aging of ANT. Possibility of crosslinkage between NF protein and contribution of pathological factors as the cause of ANT formation were discussed.

Key words

Alzheimer's neurofibrillary tangle Twisted tubule Straight tubule Neurofilament 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Adolfsson, R., Gottfries, C. G., Oreland, L., Roos, B. E., Winblad, B.: Reduced levels of catecholamines in the brain and increased activity of monamine oxidase in platelets in Alzheimer's disease: Therapeutic implications. In: Alzheimer's disease: Senile dementia and related disorders (Aging, Vol. 7). Katzman, R., Terry, R. D., Bick, K. L. (eds.), pp. 441–451 New York: Raven Press 1978Google Scholar
  2. Alzheimer, A.: Über eine eigenartige Erkrankung der Hirnrinde. Allg. Z. Psychiatr. Ihre Grenzgeb.64, 146–156 (1907)Google Scholar
  3. Bignami, A., Dahl, D.: Specificity of the glial fibrillary acidic protein for astroglia. J. Histochem. Cytochem.25, 466–469 (1977)Google Scholar
  4. Bowen, D. M., Smith, C. B., White, P., Goodhardt, M. J., Spillane, J. A., Flack, R. H. A., Davison, A. N.: Chemical pathology of the organic dementias. 1. Validity of biochemical measurements on human post-mortem brain specimens. Brain100, 397–426 (1977)Google Scholar
  5. Dahl, D.: Glial fibrillary acidic protein from bovine and rat brain. Degradation in tissues and homogenates. Biochim. Biophys. Acta420, 142–154 (1976)Google Scholar
  6. Dahl, D., Bignami, A.: Glial fibrillary acidic protein from normal and gliosed human brain. Demonstration of multiple related polypeptides. Biochim. Biophys. Acta386, 41–51 (1975a)Google Scholar
  7. Dahl, D., Bignami, A.: Protein difference associated with the loss of myelinated axons and fibrillary gliosis in rat optic nerves following Wallerian degeneration. FEBS Lett.51, 313–316 (1975b)Google Scholar
  8. Dahl, D., Bignami, A.: Immunogenic properties of the glial fibrillary acidic protein. Brain Res.116, 150–157 (1976)Google Scholar
  9. Dahl, D., Bignami, A.: Preparation of antisera to neurofilament protein from chicken brain and human sciatic nerve. J. Comp. Neurol.176, 645–658 (1977)Google Scholar
  10. Davison, P. F., Winslow, B.: The protein subunit of calf brain neurofilament. J. Neurobiol.5, 119–133 (1974)Google Scholar
  11. DeBoni, U., Crapper, D. R.: Paired helical filaments of the Alzheimer type in cultured neurons. Nature271, 566–568 (1978)Google Scholar
  12. Dziedzic, J., Iqbal, K.: Cerebral monoamine oxidase in Alzheimer dementia and Huntington chorea. Trans. Am. Soc. Neurochem.8, 271 (1977)Google Scholar
  13. Goldman, J. E., Schaumburg, H. H., Norton, W. T.: Isolation and characterization of glial filaments from human brain. J. Cell Biol.78, 426–440 (1978)Google Scholar
  14. Hirano, A., Dembitzer, H. M., Kurland, L. T., Zimmerman, H. M.: The fine structure of some intraganglionic alterations. J. Neuropathol. Exp. Neurol.27, 167–182 (1968)Google Scholar
  15. Hirano, A.: Silver impregnation of nerve cells and fibres in paraffin sections. In: An outline of neuropathology, p. 54. Tokyo: Igaku Shoin 1976 (Japanese)Google Scholar
  16. Hirano, A.: Electron microscopy in neuropathology. In: Progress in neuropathology, Zimmerman, H. M. (ed.) Vol. 1, pp. 1–61. New York, London: Grune & Stratton 1971Google Scholar
  17. Hoffman, P., Lasek, R. J.: The slow component of axonal transport. Identification of major structural polypeptides of the axon and their generality among mammalian neurons. J. Cell Biol.66, 351–366 (1975)Google Scholar
  18. Iqbal, K., Wisniewski, H. M., Shelanski, M. L., Brostoff, S., Liwnicz, B. H., Terry, R. D.: Protein changes in senile dementia. Brain Res77, 337–343 (1974)Google Scholar
  19. Iqbal, K., Grundke-Iqbal, I., Wisniewski, H. M., Terry, R. D.: Chemical relationship of the paired helical filaments of Alzheimer's dementia to normal human neurofilaments and neurotubles. Brain Res.142, 321–332 (1978a)Google Scholar
  20. Iqbal, K., Grundke-Iqubal, I., Johnson, A. B., Terry, R. D., Wisniewski, H. M.: Alzheimer neurofibrillary tangles. J. Neuropathol. Exp. Neurol.37, 633 (1978b)Google Scholar
  21. Ishii, T.: Distribution of Alzheimer's neurofibrillary changes in the brain stem and hypothalamus of senile dementia. Acta Neuropathol. (Berl.)6, 181–187 (1966)Google Scholar
  22. Ishii, T., Haga, S., Tokutake, S.: Immunofluorescence studies on localization of actin-like protein in the mouse brain. Acta Neuropathol (Berl.)42, 99–103 (1978)Google Scholar
  23. Kidd, M.: Paired helical filaments in electron microscopy of Alzheimer's disease. Nature197, 192–193 (1963)Google Scholar
  24. Klatzo, I., Wisniewski, H., Streicher, E.: Experimental production of neurofibrillary degeneration. J. Neuropathol. Exp. Neurol.24 187–199 (1965)Google Scholar
  25. Liem, R. K. H., Yen, S.-H., Salomon, G. D., Shelanski, M. L.: Intermediate filaments in nervous tissues. J. Cell Biol.79, 637–645 (1978)Google Scholar
  26. Lowry, O. H., Rosebrough, N. J., Farrand, A. L., Randall, R. J.: Protein measurement with the folin phenol reagent. J. Biol. Chem.193, 265–275 (1951)Google Scholar
  27. Nishimura, T., Hariguchi, S., Tada, K., Kaneko, Z.: Changes in brain water-soluble proteins in presenile and senile dementia. Proc. of the Int. Congress of Neuropathol. Budapest, Sept. 1–7, 1974Google Scholar
  28. Oyanagi, Sh.: Electron microscopic observations on the brains of patients with senile dementia: Conversion of neurofilaments to twisted tubules and interrelations between Alzheimer's neurofibrillary tangles and Pick's bodies. Adv. Neurol. Sci.18, 77–88 (1974) (Japanese)Google Scholar
  29. Sandler, M., Youdim, M. B. H.: Multiple formes of monoamine oxidase: Functional significance. Pharmacol. Rev.24, 331–348 (1972)Google Scholar
  30. Schlaepfer W. W.: Immunological and ultrastructural studies of neurofilaments isolated from rat peripheral nerve. J. Cell Biol.74, 226–240 (1977)Google Scholar
  31. Schlaepfer, W. W.: Deformation of isolated neurofilaments and the pathogenesis of neurofibrillary pathology. J. Neuropathol. Exp. Neurol.37, 244–254 (1978)Google Scholar
  32. Schlaepfer, W. W., Lynch, R. G.: Immunofluorescence studies of neurofilaments in the rat and human peripheral and central nervous system. J. Cell Biol.74, 241–250 (1977)Google Scholar
  33. Shelanski, M. L., Wisniewski, H.: Neurofibrillary degeneration induced by Vincristin therapy. Arch. Neurol.20, 199–206 (1969)Google Scholar
  34. Shelanski, M. L., Albert, S., DeVries, G. H., Norton, W. T.: Isolation of filaments from brain. Science174, 1242–1245 (1971)Google Scholar
  35. Shelanski, M. L., Liem, R. K. H., Selkoe, D.: The neurofilament and glial filament are biochemically distinct. J. Neuropathol. Exp. Neurol.37, 574 (1978)Google Scholar
  36. Shibayama, H., Kitoh, J.: Electron microscopic structure of the Alzheimer's neurofibrillary changes in case of atypical senile dementia. Acta Neuropathol. (Berl.)41, 229–234 (1978)Google Scholar
  37. Siegel, R. C., Martin, G. R.: Collagen cross-linking: Enzymatic synthesis of lysine-derived aldehydes and the production of cross-linked compounds. J. Biol. Chem.245, 1653–1658 (1970)Google Scholar
  38. Tanzer, M. L.: Cross-linking of collagen. Endogenous aldehydes in collagen react in several ways to from a variety of unique covalent cross-links. Science180, 561–566 (1973)Google Scholar
  39. Terry, R. D.: The fine structure of neurofibrillary tangles in Alzheimer's disease. J. Neuropathol. Exp. Neurol.22, 629–642 (1963)Google Scholar
  40. Weber, K., Osborn, M.: The reliability of molecular weight determinations by dodecyl sulfate polyacrylamide gel electrophoresis. J. Biol. Chem.244, 4406–4412 (1969)Google Scholar
  41. Wiśniewski, H., Terry, R. D.: Experimental colchicine encephalopathy. Lab. Invest.17, 577–587 (1967)Google Scholar
  42. Wisniewski, H. M., Narang, H. K., Terry, R. D.: Neurofibrillary tangles of paired helical filaments. J. Neurol. Sci.27, 173–181 (1976)Google Scholar
  43. Yen, S. H., Dahl, D., Schachner, M., Shelanski, M. L.: Biochemistry of the filaments of brain. Proc. Natl. Acad. Sci. USA73, 529–533 (1976)Google Scholar

Copyright information

© Springer-Verlag 1979

Authors and Affiliations

  • Tsuyoshi Ishii
    • 1
  • Seiichi Haga
    • 1
  • Satoshi Tokutake
    • 1
  1. 1.Psychiatric Research Institute of TokyoTokyoJapan

Personalised recommendations