The interaction between
iron and
copper has been discussed in association with human health and diseases for many years.
Ceruloplasmin, a multi-
copper oxidase, is mainly involved in
iron metabolism and its genetic defect,
aceruloplasminemia (ACP), shows
neurological disorders and diabetes associated with excessive
iron accumulation, but little is known about the state of
copper in the brain. Here, we investigated localization of these metals in the brains of three patients with ACP using electron microscopes equipped with an energy-dispersive x-ray analyzer. Histochemically,
iron deposition was observed mainly in the basal ganglia and dentate nucleus, and to lesser degree in the cerebral cortex of the patients, whereas
copper grains were not detected. X-ray microanalysis identified two types of
iron-rich particles in their brains: dense bodies, namely
hemosiderins, and their aggregated inclusions. A small number of
hemosiderins and most inclusions contained a significant amount of
copper which was enough for distinct Cu x-ray images. These
copper-containing particles were observed more frequently in the putamen and dentate nucleus than the cerebral cortex. Coexistence of
iron and
copper was supported by good correlations in the molecular ratios between these two metals in
iron-rich particles with Cu x-ray image.
Iron-dependent
copper accumulation in
iron-rich particles may suggest that
copper recycling is enhanced to meet the increased requirement of cuproproteins in
iron overload brain. In conclusion, the
iron-rich particles with Cu x-ray image were found in the ACP brain.