Analytical and Bioanalytical Chemistry

, Volume 405, Issue 6, pp 1809-1820

First online:

Opportunities in multidimensional trace metal imaging: taking copper-associated disease research to the next level

  • Stefan VogtAffiliated withX-ray Science Division, Advanced Photon Source, Argonne National Laboratory
  • , Martina RalleAffiliated withDepartment of Biochemistry and Molecular Biology, Oregon Health & Science University Email author 

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Copper plays an important role in numerous biological processes across all living systems predominantly because of its versatile redox behavior. Cellular copper homeostasis is tightly regulated and disturbances lead to severe disorders such as Wilson disease and Menkes disease. Age-related changes of copper metabolism have been implicated in other neurodegenerative disorders such as Alzheimer disease. The role of copper in these diseases has been a topic of mostly bioinorganic research efforts for more than a decade, metal–protein interactions have been characterized, and cellular copper pathways have been described. Despite these efforts, crucial aspects of how copper is associated with Alzheimer disease, for example, are still only poorly understood. To take metal-related disease research to the next level, emerging multidimensional imaging techniques are now revealing the copper metallome as the basis to better understand disease mechanisms. This review describes how recent advances in X-ray fluorescence microscopy and fluorescent copper probes have started to contribute to this field, specifically in Wilson disease and Alzheimer disease. It furthermore provides an overview of current developments and future applications in X-ray microscopic methods.

3 mm × 3 mm P, Fe, and Cu elemental maps of a lateral ventricle from a mouse brain. An H & E image is shown for comparison. The images are displayed as red temperature maps where lighter color indicates higher elemental concentration. The image emphasizes the power of XFM: the copper distribution around the lateral ventricle is extremely heterogenous with local copper concentrations exceeding 25 mM while the average is approximately 100 μM.


Imaging X-ray Fluorescence Copper Neurological disease