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

5 years ago

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

Graham N. George, Nicholas Fimognari, Virginie Lam, Ashley Hollings, Ingrid J. Pickering, David Paterson, Kelly L. Summers, Hugh H. Harris, Ryu Takechi, Mark J. Tobin, Rebecca J. Tidy, Mark J. Hackett, John C. Mamo, Mitchell Kiernan

Alzheimer’s disease (AD) is a major international health and economic concern. A key pathological feature of AD is so-called “amyloid-β-plaques”, or “Aβ-plaques”, which are deposits of aggregated protein, enriched with the Aβ fragment of amyloid precursor protein. Despite their name, the deposits are not pure Aβ 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 Aβ-plaques are a cause or a consequence of AD pathology. Further characterization of the elemental and biochemical composition within and surrounding Aβ-plaques, and knowledge of how composition varies with disease state or progression, may provide important insight into the relationship between Aβ-plaques and AD pathology. With this aim in mind, herein we demonstrate a multimodal spectroscopic imaging workflow to better characterize the complex composition of Aβ-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 Aβ-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 Aβ-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).

Publisher URL: http://dx.doi.org/10.1021/acs.biochem.7b00262

DOI: 10.1021/acs.biochem.7b00262