Memory loss occurs during natural ageing, neurodegenerative disease, or following brain injury, and has limited treatment options. The lack of effective therapies can be attributed in part to an incomplete understanding of how ageing, disease, or injury perturbs brain chemistry. Metal ions are known to be essential for healthy brain function, and at the bulk tissue level, altered levels of metal ions have been associated with disease pathology. Specifically, elevated levels of ions of Fe, Cu, and Zn are frequently associated with brain ageing, Alzheimer’s and Parkinsons disease.1,2
Characterizing different chemical forms of metal ions that are altered in brain tissue during natural ageing and brain disease has long been an analytical challenge. X-ray fluorescence microscopy (XFM) and X-ray absorption near edge structure (XANES) spectroscopy have well recognized capability to visualize metal ion distribution (XFM) and speciation (XANES) in situ, within cells and tissues. To this extent, our research team have been developing analytical protocols to visualize Fe, Cu, and Zn within brain tissue sections, i.e., visualizing the “neurometallome” (Figure 1).3-6
Through application of a multi-modal approach, incorporating XFM, XANES spectroscopy, and immuno-fluorescence, we have been able to associate metal ion accumulation with increased markers of brain inflammation in brain white matter, during ageing.7-9 Unexpectedly, we did not observe increased metal ion content within hippocampal neurons in wild type mice, and in fact saw a reduction in metal ion content of neurons in an accelerated ageing mouse model. This presentation will discuss our recent development of XFM and XANES spectroscopic protocols, and their application to study the “neurometallome” in animal models of ageing and disease.