Using energy-dispersive x-ray analysis on an electron microscope working in the scanning transmission electron microscopy mode equipped with a microanalysis system, we studied the subcellular distribution of
trace elements in
neuromelanin-containing neurons of the substantia nigra
zona compacta (SNZC) of three cases of
idiopathic Parkinson's disease (PD) [one with
Alzheimer's disease (AD)] and of three controls, in Lewy bodies of SNZC, and in synthetic
dopamine-melanin chemically charged or uncharged with Fe. Weak but significant Fe peaks similar to those of a synthetic
melanin-Fe3+ complex were seen only in intraneuronal highly electron-dense
neuromelanin granules of SNZC cells of PD brains, with the highest levels in a case of PD plus AD, whereas a synthetic
melanin-Fe2+ complex showed much lower
iron peaks, indicating that
neuromelanin has higher affinity for Fe3+ than for Fe2+. No detectable Fe was seen in nonmelanized cytoplasm of SNZC neurons and in the adjacent neuropil in both PD and controls, in Lewy bodies in SNZC neurons in PD, and in synthetic
dopamine-melanin uncharged with
iron. These findings, demonstrating for the first time a
neuromelanin-
iron complex in dopaminergic SNZC neurons in PD, support the assumption that an
iron-
melanin interaction contributes significantly to dopaminergic neurodegeneration in PD and PD plus AD.