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

Authors

  • Victoria M. Perreau,

    Corresponding author
    1. Neuroproteomics and Neurogenomics Platform, National Neurosciences Facility, The University of Melbourne, Parkville, VIC, Australia
    2. Centre for Neurosciences, The University of Melbourne, Parkville, VIC, Australia
    3. Mental Health Research Institute, The University of Melbourne, Parkville, VIC, Australia
    • Center for Neurosciences, The University of Melbourne, Parkville, Victoria 3010, Australia Fax: +61-3-9349-5917
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  • Sandra Orchard,

    1. European Bioinformatics Institute, Hinxton, Cambridge, UK
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  • Paul A. Adlard,

    1. Mental Health Research Institute, The University of Melbourne, Parkville, VIC, Australia
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  • Shayne A. Bellingham,

    1. Mental Health Research Institute, The University of Melbourne, Parkville, VIC, Australia
    2. Department of Biochemistry and Molecular Biology, The University of Melbourne, Parkville, VIC, Australia
    3. Department of Genetics, The University of Melbourne, Parkville, VIC, Australia
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  • Roberto Cappai,

    1. Department of Pathology, The University of Melbourne, Parkville, VIC, Australia
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  • Giuseppe D. Ciccotosto,

    1. Mental Health Research Institute, The University of Melbourne, Parkville, VIC, Australia
    2. Department of Pathology, The University of Melbourne, Parkville, VIC, Australia
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  • Tiffany F. Cowie,

    1. Neuroproteomics and Neurogenomics Platform, National Neurosciences Facility, The University of Melbourne, Parkville, VIC, Australia
    2. Department of Pathology, The University of Melbourne, Parkville, VIC, Australia
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  • Peter J. Crouch,

    1. Centre for Neurosciences, The University of Melbourne, Parkville, VIC, Australia
    2. Mental Health Research Institute, The University of Melbourne, Parkville, VIC, Australia
    3. Department of Pathology, The University of Melbourne, Parkville, VIC, Australia
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  • James A. Duce,

    1. Mental Health Research Institute, The University of Melbourne, Parkville, VIC, Australia
    2. Department of Pathology, The University of Melbourne, Parkville, VIC, Australia
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  • Genevieve Evin,

    1. Mental Health Research Institute, The University of Melbourne, Parkville, VIC, Australia
    2. Department of Pathology, The University of Melbourne, Parkville, VIC, Australia
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  • Noel G. Faux,

    1. Mental Health Research Institute, The University of Melbourne, Parkville, VIC, Australia
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  • Andrew F. Hill,

    1. Mental Health Research Institute, The University of Melbourne, Parkville, VIC, Australia
    2. Department of Biochemistry and Molecular Biology, The University of Melbourne, Parkville, VIC, Australia
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  • Ya Hui Hung,

    1. Centre for Neurosciences, The University of Melbourne, Parkville, VIC, Australia
    2. Mental Health Research Institute, The University of Melbourne, Parkville, VIC, Australia
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  • Simon A. James,

    1. Mental Health Research Institute, The University of Melbourne, Parkville, VIC, Australia
    2. School of Chemistry, The University of Melbourne, Parkville, VIC, Australia
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  • Qiao-Xin Li,

    1. Centre for Neurosciences, The University of Melbourne, Parkville, VIC, Australia
    2. Mental Health Research Institute, The University of Melbourne, Parkville, VIC, Australia
    3. Department of Pathology, The University of Melbourne, Parkville, VIC, Australia
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  • Su San Mok,

    1. Mental Health Research Institute, The University of Melbourne, Parkville, VIC, Australia
    2. Department of Pathology, The University of Melbourne, Parkville, VIC, Australia
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  • Deborah J. Tew,

    1. Mental Health Research Institute, The University of Melbourne, Parkville, VIC, Australia
    2. Department of Pathology, The University of Melbourne, Parkville, VIC, Australia
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  • Anthony R. White,

    1. Centre for Neurosciences, The University of Melbourne, Parkville, VIC, Australia
    2. Department of Pathology, The University of Melbourne, Parkville, VIC, Australia
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  • Ashley I. Bush,

    1. Mental Health Research Institute, The University of Melbourne, Parkville, VIC, Australia
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  • Henning Hermjakob,

    1. European Bioinformatics Institute, Hinxton, Cambridge, UK
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  • Colin L. Masters

    1. Neuroproteomics and Neurogenomics Platform, National Neurosciences Facility, The University of Melbourne, Parkville, VIC, Australia
    2. Centre for Neurosciences, The University of Melbourne, Parkville, VIC, Australia
    3. Mental Health Research Institute, The University of Melbourne, Parkville, VIC, Australia
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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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