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.

  • Brief Communication
  • Published:

Cystatin C inhibits amyloid-β deposition in Alzheimer's disease mouse models

Nature Genetics volume 39, pages 1440–1442 (2007)Cite this article

Abstract

Using transgenic mice expressing human cystatin C (encoded by CST3), we show that cystatin C binds soluble amyloid-β peptide and inhibits cerebral amyloid deposition in amyloid-β precursor protein (APP) transgenic mice. Cystatin C expression twice that of the endogenous mouse cystatin C was sufficient to substantially diminish amyloid-β deposition. Thus, cystatin C has a protective role in Alzheimer's disease pathogenesis, and modulation of cystatin C concentrations may have therapeutic implications for the disease.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1: APP overexpression diminishes cystatin C (CysC) dimerization.
Figure 2: Cystatin C (CysC) overexpression robustly decreased amyloid-β plaque load in APP and CysC double transgenic mice compared with APP singly transgenic mice.

Similar content being viewed by others

References

  1. Levy, E., Jaskolski, M. & Grubb, A. Brain Pathol. 16, 60–70 (2006).

    Article  CAS  Google Scholar 

  2. Vinters, H.V., Nishimura, G.S., Secor, D.L. & Pardridge, W.M. Am. J. Pathol. 137, 233–240 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Maruyama, K., Ikeda, S., Ishihara, T., Allsop, D. & Yanagisawa, N. Stroke 21, 397–403 (1990).

    Article  CAS  Google Scholar 

  4. Itoh, Y., Yamada, M., Hayakawa, M., Otomo, E. & Miyatake, T. J. Neurol. Sci. 116, 135–141 (1993).

    Article  CAS  Google Scholar 

  5. Levy, E. et al. J. Neuropathol. Exp. Neurol. 60, 94–104 (2001).

    Article  CAS  Google Scholar 

  6. Benussi, L. et al. Neurobiol. Dis. 13, 15–21 (2003).

    Article  CAS  Google Scholar 

  7. Paraoan, L. et al. Traffic 5, 884–895 (2004).

    Article  CAS  Google Scholar 

  8. Sastre, M. et al. Neurobiol. Aging 25, 1033–1043 (2004).

    Article  CAS  Google Scholar 

  9. Pawlik, M. et al. J. Mol. Neurosci. 22, 13–18 (2004).

    Article  Google Scholar 

  10. Hsiao, K. et al. Science 274, 99–102 (1996).

    Article  CAS  Google Scholar 

  11. Sturchler-Pierrat, C. et al. Proc. Natl. Acad. Sci. USA 94, 13287–13292 (1997).

    Article  CAS  Google Scholar 

  12. Levy, E., Lopez-Otin, C., Ghiso, J., Geltner, D. & Frangione, B. J. Exp. Med. 169, 1771–1778 (1989).

    Article  CAS  Google Scholar 

  13. Gudmundsson, G., Hallgrimsson, J., Jonasson, T.A. & Bjarnason, O. Brain 95, 387–404 (1972).

    Article  CAS  Google Scholar 

  14. Madero, M., Sarnak, M.J. & Stevens, L.A. Curr. Opin. Nephrol. Hypertens. 15, 610–616 (2006).

    Article  CAS  Google Scholar 

  15. Ghidoni, R. et al. Neurobiol. Aging 28, 371–376 (2006).

    Article  Google Scholar 

Download references

Acknowledgements

We acknowledge financial support from the US National Institute of Neurological Disorders and Stroke (NS42029), National Institute on Aging (AG017617) and American Heart Association (0040102N). We thank M. Staufenbiel for APP23 transgenic mice, K. Hsiao Ashe for Tg2576 transgenic mice, and J. Berger and M. Mazzella for technical assistance.

Author information

Author notes

  1. Magdalena Sastre & Sonia S Jung

    Present address: Present addresses: Department of Cellular and Molecular Neuroscience, Imperial College London, London W12 0NN, UK (M.S.) and Centocor Research and Development Inc., Radnor, Pennsylvania 19087, USA (S.S.J.).,

Authors and Affiliations

  1. Nathan S. Kline Institute, Orangeburg, 10962, New York, USA

    Weiqian Mi, Monika Pawlik, Sonia S Jung, David S Radvinsky, Andrew M Klein, John Sommer, Stephen D Schmidt, Ralph A Nixon, Paul M Mathews & Efrat Levy

  2. Department of Pharmacology, New York University School of Medicine, New York, 10016, New York, USA

    Monika Pawlik, Magdalena Sastre & Efrat Levy

  3. Department of Psychiatry, New York University School of Medicine, New York, 10016, New York, USA

    Ralph A Nixon, Paul M Mathews & Efrat Levy

  4. Department of Cell Biology, New York University School of Medicine, New York, 10016, New York, USA

    Ralph A Nixon

Authors
  1. Weiqian Mi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Monika Pawlik
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Magdalena Sastre
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sonia S Jung
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. David S Radvinsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Andrew M Klein
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. John Sommer
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Stephen D Schmidt
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ralph A Nixon
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Paul M Mathews
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Efrat Levy
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

W.M., with the help of S.S.J., performed the experimental work with the exception of the histological analyses, which were done by D.S.R., A.M.K. and J.S., and ELISA analysis, which was performed by S.D.S. The crosses between CysC and APP transgenic mice were generated by M.P. with the help of M.S. R.A.N. and P.M.M. assisted in the manuscript preparation and data interpretation. E.L. designed and supervised the study, interpreted findings and finalized the manuscript preparation.

Corresponding author

Correspondence to Efrat Levy.

Supplementary information

Supplementary Text and Figures

Supplementary Methods, Supplementary Figure 1 (PDF 253 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mi, W., Pawlik, M., Sastre, M. et al. Cystatin C inhibits amyloid-β deposition in Alzheimer's disease mouse models. Nat Genet 39, 1440–1442 (2007). https://doi.org/10.1038/ng.2007.29

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng.2007.29

This article is cited by

Search

Advanced 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