Formation of amyloid-like fibrils in COS cells overexpressing part of the Alzheimer amyloid protein precursor (original) (raw)

Nature volume 347, pages 566–569 (1990)Cite this article

Abstract

A PATHOLOGICAL hallmark of Alzheimer's disease is the deposition of amyloid fibrils in the brain. The principal component of the amyloid fibril is β/A4 protein1,2, which is derived from a large membrane-bound glycoprotein, Alzheimer amyloid protein precursor (APP)3. Although the deposition of amyloid is thought to result from the aberrant processing of APP, the detailed molecular mechanisms of amyloidogenesis remain unclear. A C-terminal fragment of APP which spans the β/A4 and cytoplasmic domains has a tendency to self-aggregate4,5. In an attempt to establish a cultured-cell model for amyloid fibril formation, we have trans-fected COS-1 cells with complementary DNA encoding the C-terminal 100 residues of APP. In the perinuclear regions of a small population of DNA-transfected cells, we observed inclusion-like deposits which showed a strong immunohistochemical reaction towards an anti-C-terminal APP antibody or an anti-β/A4 amyloid core-specific antibody. Electron microscope observations of the inclusion-carrying cells revealed an accumulation of amyloid-like fibrils of 8–22 nm diameter near and on the nuclear membrane. The fibrils showed a beaded or helical structure, and reacted positively with the anti-C-terminus antibody by immunoelectron microscopy. These results suggest that the formation of amyloid fibrils is an inherent characteristic of the C-terminal peptide of APP. The present system provides a suitable model for the molecular dissection of the process of brain amyloidogenesis.

This is a preview of subscription content, access via your institution

Access options

Subscribe to this journal

Receive 51 print issues and online access

$199.00 per year

only $3.90 per issue

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Additional access options:

Similar content being viewed by others

References

  1. Glenner, G. G. & Wong, C. W. Biochem. biophys. Res. Commun. 122, 1131–1135 (1984).
    Article CAS Google Scholar
  2. Masters, C. L. et al. Proc. natn. Acad. Sci. U.S.A. 82, 4245–4249 (1985).
    Article ADS CAS Google Scholar
  3. Kang, J. et al. Nature 325, 733–736 (1987).
    Article ADS CAS Google Scholar
  4. Dyrks, T. et al. EMBO J. 7, 949–957 (1988).
    Article CAS Google Scholar
  5. Wolf, D. et al. EMBO J. 9, 2079–2084 (1990).
    Article CAS Google Scholar
  6. Yoshikawa, K., Williams, C. & Sabol, S. L. J. biol. Chem. 259, 14301–14308 (1984).
    Article CAS Google Scholar
  7. Wong, G. G. et al. Science 228, 810–815 (1985).
    Article ADS CAS Google Scholar
  8. Ishii, T., Kametani, F., Haga, S. & Sato, M. Neuropath. appl. Neurobiol. 15, 135–147 (1989).
    Article CAS Google Scholar
  9. Kidd, M. Brain 87, 307–320 (1964).
    Article CAS Google Scholar
  10. Terry, R. D., Gonatas, N. K. & Weiss, M. Am. J. Pathol. 44, 269–283 (1964).
    CAS PubMed PubMed Central Google Scholar
  11. Merz, P. A. et al. Acta neuropathol. 60, 113–124 (1983).
    Article CAS Google Scholar
  12. Miyakawa, T., Katsuragi, S., Watanabe, K., Shimoji, A. & Ikeuchi, Y. Acta neuropathol. 70, 202–208 (1986).
    Article CAS Google Scholar
  13. Miyakawa, T., Watanabe, K. & Katsuragi, S. Virchows Arch. 52, 99–106 (1986).
    Article CAS Google Scholar
  14. Kirschner, D. A. et al. Proc. natn. Acad. Sci. U.S.A. 84, 6953–6957 (1987).
    Article ADS CAS Google Scholar
  15. Sisodia, S. S., Koo, E. H., Beyreuther, K., Unterbeck, A. & Price, D. L. Science 248, 492–495 (1990).
    Article ADS CAS Google Scholar
  16. Esch, F. S. et al. Science 248, 1122–1124 (1990).
    Article ADS CAS Google Scholar
  17. Yankner, B. A. et al. Science 245, 417–429 (1989).
    Article ADS CAS Google Scholar
  18. Selkoe, D. J. et al. Proc. natn. Acad. Sci. U.S.A. 85, 7341–7345 (1988).
    Article ADS CAS Google Scholar
  19. Weidemann, A. et al. Cell 57, 115–126 (1989).
    Article CAS Google Scholar
  20. Saitoh, T. et al. Cell 58, 615–622 (1989).
    Article CAS Google Scholar
  21. Marotta, C. A. et al. Proc. natn. Acad. Sci. U.S.A. 86, 337–341 (1989).
    Article ADS CAS Google Scholar
  22. Robakis, N. K., Ramakrishna, N., Wolfe, G. & Wisniewski, H. M. Proc. natn. Acad. Sci. U.S.A. 84, 4190–4194 (1987).
    Article ADS CAS Google Scholar
  23. Kunkel, T. A. Proc. natn. Acad. Sci. U.S.A. 82, 488–492 (1988).
    Article ADS Google Scholar
  24. Brandl, C. J., deLeon, S., Martin, D. R. & MacLennan, D. H. J. biol. Chem. 262, 3768–3774 (1987).
    Article CAS Google Scholar
  25. Sanger, F., Nicklen, S. & Coulson, A. R. Proc. natn. Acad. Sci. U.S.A. 74, 5463–5467 (1977).
    Article ADS CAS Google Scholar
  26. Sompayrac, L. M. & Danna, K. J. Proc. natn. Acad. Sci. U.S.A. 78, 7575–7578 (1981).
    Article ADS CAS Google Scholar
  27. Maruyama, K. & MacLennan, D. H. Proc. natn. Acad. Sci. U.S.A. 85, 3314–3318 (1988).
    Article ADS CAS Google Scholar
  28. Laemmli, U. K. Nature 227, 680–685 (1970).
    Article ADS CAS Google Scholar
  29. Springer, T. A. J. biol. Chem. 256, 3833–3839 (1981).
    Article CAS Google Scholar

Download references

Author information

Author notes

  1. Kiyoshi Terakado: Department of Regulation Biology, Faculty of Science, University of Saitama, Urawa 338, Japan

Authors and Affiliations

  1. Department of Molecular Biology, Psychiatric Research Institute of Tokyo, Setagaya-ku, Tokyo, 156, Japan
    Kei Maruyama, Kiyoshi Terakado, Mihoko Usami & Kazuaki Yoshikawa

Authors

  1. Kei Maruyama
    You can also search for this author inPubMed Google Scholar
  2. Kiyoshi Terakado
    You can also search for this author inPubMed Google Scholar
  3. Mihoko Usami
    You can also search for this author inPubMed Google Scholar
  4. Kazuaki Yoshikawa
    You can also search for this author inPubMed Google Scholar

Rights and permissions

About this article

Cite this article

Maruyama, K., Terakado, K., Usami, M. et al. Formation of amyloid-like fibrils in COS cells overexpressing part of the Alzheimer amyloid protein precursor.Nature 347, 566–569 (1990). https://doi.org/10.1038/347566a0

Download citation

This article is cited by