Research Article

A domain level interaction network of amyloid precursor protein and Aβ of Alzheimer's disease

  1. Victoria M. Perreau1,2,3,*,
  2. Sandra Orchard4,
  3. Paul A. Adlard3,
  4. Shayne A. Bellingham3,5,6,
  5. Roberto Cappai7,
  6. Giuseppe D. Ciccotosto3,7,
  7. Tiffany F. Cowie1,7,
  8. Peter J. Crouch2,3,7,
  9. James A. Duce3,7,
  10. Genevieve Evin3,7,
  11. Noel G. Faux3,
  12. Andrew F. Hill3,5,
  13. Ya Hui Hung2,3,
  14. Simon A. James3,8,
  15. Qiao-Xin Li2,3,7,
  16. Su San Mok3,7,
  17. Deborah J. Tew3,7,
  18. Anthony R. White2,7,
  19. Ashley I. Bush3,
  20. Henning Hermjakob4,
  21. Colin L. Masters1,2,3

Article first published online: 13 APR 2010

DOI: 10.1002/pmic.200900773

Issue

PROTEOMICS

PROTEOMICS

Volume 10, Issue 12, pages 2377–2395, No. 12 June 2010

Additional Information

How to Cite

Perreau, V. M., Orchard, S., Adlard, P. A., Bellingham, S. A., Cappai, R., Ciccotosto, G. D., Cowie, T. F., Crouch, P. J., Duce, J. A., Evin, G., Faux, N. G., Hill, A. F., Hung, Y. H., James, S. A., Li, Q.-X., Mok, S. S., Tew, D. J., White, A. R., Bush, A. I., Hermjakob, H. and Masters, C. L. (2010), A domain level interaction network of amyloid precursor protein and Aβ of Alzheimer's disease. Proteomics, 10: 2377–2395. doi: 10.1002/pmic.200900773

Author Information

  1. 1

    Neuroproteomics and Neurogenomics Platform, National Neurosciences Facility, The University of Melbourne, Parkville, VIC, Australia

  2. 2

    Centre for Neurosciences, The University of Melbourne, Parkville, VIC, Australia

  3. 3

    Mental Health Research Institute, The University of Melbourne, Parkville, VIC, Australia

  4. 4

    European Bioinformatics Institute, Hinxton, Cambridge, UK

  5. 5

    Department of Biochemistry and Molecular Biology, The University of Melbourne, Parkville, VIC, Australia

  6. 6

    Department of Genetics, The University of Melbourne, Parkville, VIC, Australia

  7. 7

    Department of Pathology, The University of Melbourne, Parkville, VIC, Australia

  8. 8

    School of Chemistry, The University of Melbourne, Parkville, VIC, Australia

*Center for Neurosciences, The University of Melbourne, Parkville, Victoria 3010, Australia Fax: +61-3-9349-5917

Publication History

  1. Issue published online: 15 JUN 2010
  2. Article first published online: 13 APR 2010
  3. Manuscript Accepted: 27 MAR 2010
  4. Manuscript Revised: 23 MAR 2010
  5. Manuscript Received: 23 NOV 2009

Funded by

  • NHMRC

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Keywords:

  • Alzheimer's disease;
  • Amyloid precursor protein;
  • Protein–protein interaction;
  • Systems biology

Abstract

The primary constituent of the amyloid plaque, β-amyloid (Aβ), is thought to be the causal “toxic moiety” of Alzheimer's disease. However, despite much work focused on both Aβ and its parent protein, amyloid precursor protein (APP), the functional roles of APP and its cleavage products remain to be fully elucidated. Protein–protein interaction networks can provide insight into protein function, however, high-throughput data often report false positives and are in frequent disagreement with low-throughput experiments. Moreover, the complexity of the CNS is likely to be under represented in such databases. Therefore, we curated the published work characterizing both APP and Aβ to create a protein interaction network of APP and its proteolytic cleavage products, with annotation, where possible, to the level of APP binding domain and isoform. This is the first time that an interactome has been refined to domain level, essential for the interpretation of APP due to the presence of multiple isoforms and processed fragments. Gene ontology and network analysis were used to identify potentially novel functional relationships among interacting proteins.

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