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    Amyloid-ß and islet amyloid pathologies link Alzheimer disease and type 2 diabetes in a transgenic model.

    Access Status
    Open access via publisher
    Authors
    Wijesekara, N.
    Ahrens, R.
    Sabale, M.
    Wu, L.
    Ha, K.
    Verdile, Giuseppe
    Fraser, P.
    Date
    2017
    Type
    Journal Article
    
    Metadata
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    Citation
    Wijesekara, N. and Ahrens, R. and Sabale, M. and Wu, L. and Ha, K. and Verdile, G. and Fraser, P. 2017. Amyloid-ß and islet amyloid pathologies link Alzheimer disease and type 2 diabetes in a transgenic model. The FASEB Journal. 31 (12): 5409-5418.
    Source Title
    The FASEB Journal
    DOI
    10.1096/fj.201700431R
    ISSN
    1530-6860
    School
    School of Biomedical Sciences
    URI
    http://hdl.handle.net/20.500.11937/56653
    Collection
    • Curtin Research Publications
    Abstract

    Alzheimer's disease (AD) and type 2 diabetes (T2D) present a significant risk to each other. AD and T2D are characterized by deposition of cerebral amyloid-ß (Aß) and pancreatic human islet amyloid polypeptide (hIAPP), respectively. We investigated the role of amyloidogenic proteins in the interplay between these diseases. A novel double transgenic mouse model combining T2D and AD was generated and characterized. AD-related amyloid transgenic mice coexpressing hIAPP displayed peripheral insulin resistance, hyperglycemia, and glucose intolerance. Aß and IAPP amyloid co-deposition increased tau phosphorylation, and a reduction in pancreatic ß-cell mass was detected in islets. Increased brain Aß deposition and tau phosphorylation and reduced insulin levels and signaling were accompanied by extensive synaptic loss and decreased neuronal counts. Aß immunization rescued the peripheral insulin resistance and hyperglycemia, suggesting a role for Aß in T2D pathogenesis for individuals predisposed to AD. These findings demonstrate that Aß and IAPP are key factors in the overlapping pathologies of AD and T2D.-Wijesekara, N., Ahrens, R., Sabale, M., Wu, L., Ha, K., Verdile, G., Fraser, P. E. Amyloid-ß and islet amyloid pathologies link Alzheimer disease and type 2 diabetes in a transgenic model.

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