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.

APP locus duplication causes autosomal dominant early-onset Alzheimer disease with cerebral amyloid angiopathy

Abstract

We report duplication of the APP locus on chromosome 21 in five families with autosomal dominant early-onset Alzheimer disease (ADEOAD) and cerebral amyloid angiopathy (CAA). Among these families, the duplicated segments had a minimal size ranging from 0.58 to 6.37 Mb. Brains from individuals with APP duplication showed abundant parenchymal and vascular deposits of amyloid-β peptides. Duplication of the APP locus, resulting in accumulation of amyloid-β peptides, causes ADEOAD with CAA.

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

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: APP locus duplication in five kindreds.
Figure 2: Immunochemical characterization of CAA and senile plaques in brain tissues of a patient from family F037.

References

  1. Tanzi, R.E. et al. Cell 120, 545–555 (2005).

    Article  CAS  Google Scholar 

  2. Vonsattel, J.P. et al. Ann. Neurol. 30, 637–649 (1991).

    Article  CAS  Google Scholar 

  3. Tournier, I. et al. Cancer Res. 64, 8143–8147 (2004).

    Article  CAS  Google Scholar 

  4. Raux, G. et al. J. Med. Genet. 42, 793–795 (2005).

    Article  CAS  Google Scholar 

  5. Rahmani, Z. et al. Proc. Natl. Acad. Sci. USA 86, 5958–5962 (1989).

    Article  CAS  Google Scholar 

  6. Sharp, A.J. et al. Am. J. Hum. Genet. 77, 78–88 (2005).

    Article  CAS  Google Scholar 

  7. Hattori, M. et al. Nature 405, 311–319 (2000).

    Article  CAS  Google Scholar 

  8. Jackson, J.F. et al. Clin. Genet. 9, 483–487 (1976).

    Article  CAS  Google Scholar 

  9. Braak, H. et al. Acta Neuropathol. (Berl.) 82, 239–259 (1991).

    Article  CAS  Google Scholar 

  10. Mirra, S.S. et al. Neurology 41, 479–486 (1991).

    Article  CAS  Google Scholar 

  11. Tapiola, T. et al. Neurology 56, 979–980 (2001).

    Article  CAS  Google Scholar 

  12. Oyama, F. et al. J. Neurochem. 62, 1062–1066 (1994).

    Article  CAS  Google Scholar 

  13. Prasher, V.P. et al. Ann. Neurol. 43, 380–382 (1998).

    Article  CAS  Google Scholar 

  14. Delabar, J.M. et al. Science 235, 1390–1392 (1987).

    Article  CAS  Google Scholar 

  15. Singleton, A.B. et al. Science 302, 841 (2003).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank A. Rossi, C. De La Rochebrochard and H. Moirot for cytogenetic materials, C. Duyckaerts and F. Letournel for brain tissue samples, F. Checler for antibodies to Aβ, J. Bou for technical assistance, A. Goldenberg, S. Jacquemont, E. De La Fournière, T. Dutoya, C. Thomas-Anterion and F. Pasquier for clinical evaluation of patients and M. Tosi for critical reading of the manuscript. A.R.-L. was supported by le Conseil Regional de Haute Normandie.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Dominique Campion.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Rovelet-Lecrux, A., Hannequin, D., Raux, G. et al. APP locus duplication causes autosomal dominant early-onset Alzheimer disease with cerebral amyloid angiopathy. Nat Genet 38, 24–26 (2006). https://doi.org/10.1038/ng1718

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng1718

This article is cited by

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