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    A Multimodal Spectroscopic Imaging Method To Characterize the Metal and Macromolecular Content of Proteinaceous Aggregates ("Amyloid Plaques").

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    Authors
    Summers, K.
    Fimognari, N.
    Hollings, A.
    Kiernan, M.
    Lam, Virginie
    Tidy, R.
    Paterson, D.
    Tobin, M.
    Takechi, Ryu
    George, G.
    Pickering, I.
    Mamo, J.
    Harris, H.
    Hackett, M.
    Date
    2017
    Type
    Journal Article
    
    Metadata
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    Citation
    Summers, K. and Fimognari, N. and Hollings, A. and Kiernan, M. and Lam, V. and Tidy, R. and Paterson, D. et al. 2017. A Multimodal Spectroscopic Imaging Method To Characterize the Metal and Macromolecular Content of Proteinaceous Aggregates ("Amyloid Plaques").. Biochemistry.
    Source Title
    Biochemistry
    DOI
    10.1021/acs.biochem.7b00262
    ISSN
    1520-4995
    School
    School of Public Health
    URI
    http://hdl.handle.net/20.500.11937/56158
    Collection
    • Curtin Research Publications
    Abstract

    Alzheimer's disease (AD) is a major international health and economic concern. A key pathological feature of AD is so-called "amyloid-ß-plaques", or "Aß-plaques", which are deposits of aggregated protein, enriched with the Aß fragment of amyloid precursor protein. Despite their name, the deposits are not pure Aß and have a heterogeneous, chemically complex composition that can include multiple proteins, lipids, and metal ions (Fe, Cu, or Zn). Despite extensive research, it is still uncertain whether Aß-plaques are a cause or a consequence of AD pathology. Further characterization of the elemental and biochemical composition within and surrounding Aß-plaques, and knowledge of how composition varies with disease state or progression, may provide important insight into the relationship between Aß-plaques and AD pathology. With this aim in mind, herein we demonstrate a multimodal spectroscopic imaging workflow to better characterize the complex composition of Aß-plaques. Our approach incorporates several spectroscopic imaging techniques, such as Fourier transform infrared spectroscopic imaging (FTIR), Raman microscopy, and X-ray fluorescence microscopy (XFM). While FTIR, Raman, and XFM have been used previously, mostly in isolation, to study Aß-plaques, application of all three techniques, in combination with histology and fluorescence microscopy, has not been reported previously. We demonstrate that a multimodal workflow, incorporating all three methods on adjacent or serial tissue sections, can reveal substantial complementary information about the biochemical and elemental composition of Aß-plaques. Information revealed by the method includes the relative content and distribution of aggregated protein, total lipid, lipid esters, cholesterol, and metals (Fe, Cu, or Zn).

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