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.
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Increases of iron and a decrease of ferritin in the substantia nigra are indicative of high iron loading of ferritin.
“Increases of iron and a decrease of ferritin in the substantia nigra101,116–119 are indicative of high iron loading of ferritin.120”
From The role of iron in brain ageing and neurodegenerative disorders (2014) · cites this paper as [117]
Low iron concentrations can reduce the neuronal deposits of ferritin, generating a condition in the substantia nigra neurons of patients with Parkinson's disease.
“Moreover, low iron concentrations can reduce the neuronal deposits of ferritin, generating a condition in the substantia nigra neurons of patients with Parkinson’s disease.117,119”
From The role of iron in brain ageing and neurodegenerative disorders (2014) · cites this paper as [117]
In the temporal cortex and globus pallidus of patients with Parkinson's disease, a decrease of total iron concentration was detected by inductively coupled plasma mass spectrometry.
“In the temporal cortex and globus pallidus of patients with Parkinson’s disease, a decrease of total iron concentration was detected by inductively coupled plasma mass spectrometry.101,117,130”
From The role of iron in brain ageing and neurodegenerative disorders (2014) · cites this paper as [117]
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Iron and dopamine: a toxic couple
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“Alteration in myelin and iron contents has been associated with a large number of neurological diseases, including, for example Parkinson’s diseases, Huntington’s disease, Alzheimer’s disease, and multiple sclerosis [Bartzokis, 2004a; Bitsch et al., 2000; Dexter et al., 1991].”
BackgroundThe neurotoxicity of iron, copper and manganese in Parkinson's and Wilson's diseases
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“Elevated Zn levels have been found in the SN of PD brains (74), while reduced levels of Zn in serum and plasma have been linked to an increased risk for PD (80).”
BackgroundComplex I, iron, and ferritin in Parkinson's disease substantia nigra
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“Also Dexter and coworkers [6] observed increased iron levels and concomitant rises in ferritin concentration in the substantia nigra of patients who had died from either multiplesystem atrophy or progressive supranuclear palsy.”
BackgroundSelf-citationCopper transport to the brain by the blood-brain barrier and blood-CSF barrier
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“The mRNAs encoding Cu transporter-1 (Ctr1) and ATP7A were higher in the CP than those in brain capillaries and parenchyma, whereas ATP7B mRNA was higher in brain capillaries than those in the CP and brain parenchyma.”
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“Elevated Fe and Cu deficiency have been found in the substantia nigra in PD [23,24].”
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Homeostasis and metabolism of iron and other metal ions in neurodegenerative diseases
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Self-citationIron in the basal ganglia in Parkinson's disease
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“Many authors have described ferritin as the main iron storage compound (Riederer et al., 1989; Dexter et al., 1991), and ferritin was the only detectable iron-containing compound found in Parkinson's disease and age-matched controls in the present study.”
InfluentialBrain iron deposition in Parkinson's disease imaged using the PRIME magnetic resonance sequence
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“structures of the basal ganglia (Dexter et al., 1987, 1991; Sofic et al., 1988; Riederer et al., 1989).”
BackgroundEnvironmental Exposures and Parkinson’s Disease
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The Role of Iron in Neurodegeneration: Prospects for Pharmacotherapy of Parkinson??s Disease
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Metabolic biomarkers related to oxidative stress and antioxidant status in Saudi autistic children
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- Authors
- DEXTER, D. T., CARAYON, A., JAVOY-AGID, F., AGID, Y., WELLS, F. R., DANIEL, S. E., LEES, A. J., JENNER, P., & MARSDEN, C. D.
- Affiliations
- King's College London (GB)
- Inserm (FR)
- Parkinson's UK (GB)
- Corresponding author
- JENNER, P.
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 1991
- Volume
- 114
- Issue
- 4
- Pages
- 1953-1975
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W2123913108
- Cited by
- 1,043
- References
- 0
- Citations by year
- 2026: 18 · 2025: 29 · 2024: 47 · 2023: 28 · 2022: 37 · 2021: 43 · 2020: 36 · 2019: 38 · 2018: 30 · 2017: 45 · 2016: 56 · 2015: 45 · 2014: 41 · 2013: 44 · 2012: 32
- FWCI
- 12.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Royal Society
- Topics
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Keywords
- Parkinson's disease, progressive supranuclear palsy, multiple system atrophy, Huntington's disease, basal ganglia, iron, ferritin, copper, zinc, manganese, substantia nigra, striatum, globus pallidus, neurodegeneration, trace metals, iron overload
- MeSH terms
- Aging, Atrophy, Basal Ganglia Diseases, Brain, Brain Diseases, Ferritins, Humans, Huntington Disease, Iron, Metals, Parkinson Disease, Radioimmunoassay, Reference Values, Supranuclear Palsy, Progressive, Trace Elements
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