Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Formation of β-amyloid protein deposits in brains of transgenic mice

Abstract

DEPOSITS of β-amyloid are one of the main pathological charac-teristics of Alzheimer's disease. The β-amyloid peptide constituent (relative molecular mass 4,200) of the deposits is derived from the β-amyloid precursor protein (β-APP) which is expressed in several different isoforms1–6. The two most prevalent β-APP isoforms are distinguished by either the presence (β-APP751) or absence (β-APP695) of a Kunitz serine protease inhibitor domain. Changes in the abundance of different β-APP messenger RNAs in brains of Alzheimer's disease victims have been widely reported7–12. Although these results have been controversial, most evidence favours an increase in the mRNAs encoding protease inhibitor-containing isoforms of β-APP and it is proposed that this change contributes to β -amyloid formation9–12. We have now produced an imbalance in the normal neuronal ratio of β-APP isoforms by preparing transgenic mice expressing additional β-APP751 under the control of a neural-specific promoter. The cortical and hip-pocampal brain regions of the transgenic mice display extracellular β -amyloid immunoreactive deposits varying in size (<5–50μm) and abundance. These results suggest that one mechanism of β-amyloid formation may involve a disruption of the normal ratio of neuronal β-APP isoform expression and support a direct relationship between increased expression of Kunitz inhibitor-bearing β-APP isoforms and β-amyloid deposition.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Similar content being viewed by others

References

  1. Glenner, G. G. & Wong, C. W. Biochem. biophys. Res. Commun. 120, 885–890 (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. Ponte, P. et al. Nature 331, 525–528 (1988).

    Article  ADS  CAS  Google Scholar 

  5. Tanzi, R. E. et al. Nature 331, 528–530 (1988).

    Article  ADS  CAS  Google Scholar 

  6. Kitaguchi, N., Takahashi, Y., Tokushima, Y., Shiojiri, S. & Ito, H. Nature 331, 530–532 (1988).

    Article  ADS  CAS  Google Scholar 

  7. Palmert, M. R. et al. Science 241, 1080–1084 (1988).

    Article  ADS  CAS  Google Scholar 

  8. Neve, R. L., Finch, E. A. & Dawes, L. R. Neuron 1, 669–677 (1988).

    Article  CAS  Google Scholar 

  9. Johnson, S. A. et al. Expl Neurol. 102, 264–268 (1988).

    Article  CAS  Google Scholar 

  10. Tanaka, S. et al. Biochem. biophys. Res. Commun. 157, 472–479 (1988).

    Article  CAS  Google Scholar 

  11. Johnson, S. A., McNeill, T., Cordell, B. & Finch, C. E. Science 248, 854–857 (1990).

    Article  ADS  CAS  Google Scholar 

  12. Neve, R. L., Rogers, J. & Higgens, G. A. Neuron 5, 329–338 (1990).

    Article  CAS  Google Scholar 

  13. Forss-Petter, S. et al. Neuron 5, 187–197 (1990).

    Article  CAS  Google Scholar 

  14. Shivers, B. D. et al. EMBO J. 7, 1365–1370 (1988).

    Article  CAS  Google Scholar 

  15. Takio, K., Hasegawa, M., Titani, K. & Ihara, Y. Biochem. biophys. Res. Commun. 160, 1296–1301 (1989).

    Article  CAS  Google Scholar 

  16. Murphy, G. M. et al. Prog. Neuro-psychopharmac. 14, 309–317 (1990).

    Article  Google Scholar 

  17. Goate, A. et al. Nature 349, 704–706 (1991).

    Article  ADS  CAS  Google Scholar 

  18. Yamaguchi, H., Hirai, S., Morimatsu, M., Shoji, M. & Ihara, Y. Acta neuropath. 76, 541–549 (1988).

    Article  CAS  Google Scholar 

  19. Tagliavini, F., Giaccone, G., Frangione, B. & Bugiani, O. Neurosci. Lett. 103, 191–196 (1988).

    Article  Google Scholar 

  20. Ikeda, S., Allsop, D. & Glenner, G. G. Lab. Invest. 60, 113–122 (1989).

    CAS  PubMed  Google Scholar 

  21. Bugiani, O., Giaconne, G., Frangione, B., Ghetti, B. & Tagliavini, F. Neurosci. Lett. 103, 263–268 (1989).

    Article  CAS  Google Scholar 

  22. Sakimura, K., Kushiya, E., Takahashi, Y. & Suzuki, Y. Gene 60, 103–113 (1987).

    Article  CAS  Google Scholar 

  23. Okayama, H. & Berg, P. Mol. cell. Biol. 3, 280–289 (1983).

    Article  CAS  Google Scholar 

  24. Eklund, J. & Bradford, G. E. Anim. Prod. 22, 127–130 (1976).

    Article  Google Scholar 

  25. Southern, E. M. J. molec. Biol. 98, 503–517 (1975).

    Article  CAS  Google Scholar 

  26. Saiki, R. K. et al. Science 239, 487–491 (1988).

    Article  ADS  CAS  Google Scholar 

  27. Laemmli, U. K. Nature 227, 680–685 (1970).

    Article  ADS  CAS  Google Scholar 

  28. Tobin, H., Staehelin, T. & Gordon, J. Proc. natn. Acad. Sci. U.S.A. 76, 4350–4354 (1979).

    Article  ADS  Google Scholar 

  29. Taggart, R. T. & Samloff, I. M. Science 219, 1228–1230 (1983).

    Article  ADS  CAS  Google Scholar 

  30. Allsop, D. et al. Neuropath. appl. Neurobiol. 15, 531–542 (1989).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Quon, D., Wang, Y., Catalano, R. et al. Formation of β-amyloid protein deposits in brains of transgenic mice. Nature 352, 239–241 (1991). https://doi.org/10.1038/352239a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/352239a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing