Alterations in the Levels of Iron, Ferritin and Other Trace Metals in Parkinson's Disease and Other Neurodegenerative Diseases Affecting the Basal Ganglia

Abstract

Levels of iron, copper, zinc and manganese were measured by inductively coupled plasma spectroscopy in frozen postmortem brain tissue from patients with Parkinson's disease (PD), progressive supranuclear palsy (PSP), multiple system atrophy with strionigral degeneration (MSA), and Huntington's disease (HD) compared with control subjects. Total iron levels were found to be elevated in the areas of basal ganglia showing pathological change in these disorders. In particular, total iron content was increased in substantia nigra in PD, PSP and MSA, but not in HD. Total iron levels in the striatum (putamen and/or caudate nucleus) were increased in PSP, MSA and HD but not in PD. Total iron levels were decreased in the globus pallidus in PD. There were no consistent alterations of manganese levels in basal ganglia structures in any of the diseases studied. Copper levels were decreased in the substantia nigra in PD, and in the cerebellum in PSP, and were elevated in the putamen and possibly substantia nigra in HD. Zinc levels were only increased in PD, in substantia nigra and in caudate nucleus and lateral putamen. Levels of the iron binding protein ferritin were measured in the same patient groups using a radio-immunoassay technique. Increased iron levels in basal ganglia were generally associated with normal or elevated levels of ferritin immunoreactivity, for example, the substantia nigra in PSP and possibly MSA, and in putamen in MSA. The exception was PD where there was a generalized reduction in brain ferritin immunoreactivity, even in the substantia nigra. An increase in total iron content appears to be a response to neurodegeneration in affected basal ganglia regions in a number of movement disorders. However, only in PD was there an increased total iron level, decreased ferritin content, decreased copper content, and an increased zinc concentration in substantia nigra. These findings suggest an alteration of iron handling in the substantia nigra in PD. Depending on the form in which the excess iron load exists in nigra in PD, it may contribute to the neurodegenerative process.

Epidemiology and etiology of Parkinson’s disease: a review of the evidence

“…There are also case reports on parkinsonism induced by lead exposure [376]. Iron has been hypothesized to play a role in PD based on its involvement in oxidative stress, and increased iron levels were demonstrated in the substantia nigra of PD patients compared to controls, although iron levels were also increased in patients with progressive supranuclear palsy (PSP) and MSA [377,378]. Copper and zinc are important as co-factors for the enzyme superoxide dismutase (SOD), and alterations in nigral levels of these metals have also been reported [378,379].…”

The R6 lines of transgenic mice: A model for screening new therapies for Huntington's disease

“…Metals like iron, copper or zinc, which appear to be increased in brains of HD patients (Dexter et al, 1991), may participate in the generation of reactive oxygen species and therefore promote oxidative stress. Therefore, the use of metal-binding compounds can prove to be an efficient antioxidant strategy.…”

Correlation of R2 with total iron concentration in the brains of rhesus monkeys

“…In Parkinson's disease (PD), for example, postmortem examinations of the brain have demonstrated an elevated iron concentration in the substantia nigra (4,5) and the concentration of neuromelanin, which contains iron, is higher in PD subjects than in age-matched controls (6). Other movement disorders are characterized by elevated iron levels in the basal ganglia (7,8). Ferritin, transferrin, and iron are found in the vicinity of the plaques, which are characteristic of Alzheimer's disease (9).…”