Iron in the Brain?
What are the effects of increased iron levels in the brain?
Could it be connected: To Alzheimers? To Parkinsons? To learning disabilities such as ADD, ADHD?? To other neurodegenerative disorders? Seizures, Strokes, Downs syndrome?
Click on the titles below to read studies,
abstracts & links, which consider these possibilities.
A quantitative analysis of isoferritins in select regions of aged, parkinsonian, and Alzheimer's diseased brains. J Neurochem. 1995 Aug; The brain requires a ready supply of iron for normal neurological function, but free iron is toxic. Consequently, iron bioavailability must be stringently regulated. Recent evidence has suggested that the brain iron regulatory system is dysfunctional in neurological disorders such as Alzheimer's and Parkinson's diseases.
hereditary hemochromatosis mutations involved in Alzheimer disease?
The possibility that HFE mutations are important new genetic risk factors for AD should be pursued further. Am J Med Genet 2000 Jul
iron stores and early neurologic deterioration in acute cerebral infarction
Neurology 2000 Increased body iron stores may contribute to stroke progression by enhancing the cytotoxic mechanisms in cerebral ischemia American Academy of Neurology
the controversy of the role of aluminum in Alzheimer's disease be resolved?
J Toxicol Environ Health 1996 Aug 30 At first glance, this is about aluminum-but keep reading.
distribution of transferrin, ferritin, and iron in normal and aged human brains.
J Neurosci Res 1990 Dec
Cellular management of iron in the brain J Neurol Sci 1995 Dec Changes in the cellular distribution of iron and its associated regulatory proteins occur in Alzheimer's disease.
Central nervous system and eye Barton 2000, p. 211
Chemistry and biology of eukaryotic iron metabolism. Int J Biochem Cell Biol. 2001 Oct Department of Physiology and Biophysics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY A surprising connection between iron metabolism and Friedreich's ataxia has been uncovered. It is no exaggeration to say that the new understanding of iron metabolism in health and disease has been explosive, and that what is past is likely to be prologue to what is ahead.
Clinical report of three patients with hereditary hemochromatosis and movement disorders HH should be investigated more systematically in patients with movement disorders. Mov Disord 2000 Nov
and vitamin E protect against iron and MPTP-induced neurodegeneration in mice.
J Neural Transm 1997 Our data suggested that: (1) iron may induce neuronal damage and thus excessive iron in the brain may contribute to the neuronal loss in PD; (2) iron chelators and antioxidants may serve as potential therapeutic agents in retarding the progression of neurodegeneration.
ELDERLY AMERICANS WHO HAVE EXCESS IRON IN THEIR BODY,
TAKING IRON SUPPLEMENTS IS UNNECESARRY AND MAY BE DANGEROUS
The American Society for Nutritional Sciences The American Society for Clinical Nutrition 9650 Rockville Pike, Bethesda, Maryland 20814-3998 March 2001
Fried reich's Ataxia Fact Sheet ......the finding of abnormally high levels of iron in the heart tissue of people with Friedreich's ataxia National Institute of Neurological Disorders and Stroke
A Common, Rarely Diagnosed Disease
By Vincent J. Felitti, MD, FACP Commentary by David Baer, MD, FACP. Hemochromatosis is the most common, life-threatening genetic disorder in North America, yet most physicians have never personally diagnosed a case: all see an unrecognized case in their offices every two weeks.
Hereditary haemochromatosis: a case of iron accumulation in the basal ganglia associated with a parkinsonian syndrome: J Neurol Neurosurg Psychiatry 1995 Sep Hereditary haemochromatosis should be considered in the differential diagnosis of parkinsonian syndromes, because complications of iron induced organ injury may be prevented by phlebotomy.
High Iron May Mean Worsening Stroke But U.S. specialists say Spanish study is not the last word By Adam Marcus HealthScout Reporter MONDAY, April 24, 200 (HealthScout) -- High iron levels in the blood may be an important factor in figuring out who will fare worse after a stroke. Patients with very high iron levels were about 80 percent more likely to have a type of brain damage that eroded still more after a stroke than those with levels nearly half as great. The brains of the stroke victims with less iron stabilized or grew better, according to a new study by Spanish researchers in this month's Neurology.
basal ganglia iron levels in Huntington disease
The data suggest that increased iron levels may be related to the pattern of neurotoxicity observed in HD. Reducing the oxidative stress associated with increased iron levels may offer novel ways to delay the rate of progression and possibly defer the onset of HD. Arch Neurol. 1999
Increased cerebral iron uptake in Wilson's disease: a 52Fe-citrate PET study. J Nucl Med 2000 May Toxicity of abundant copper is the main cause of brain and liver tissue damage in patients with Wilson's disease (WD). However, there is also evidence of a disturbed iron metabolism in this genetically determined disorder.
Influence of ferritin levels on LDL cholesterol concentration
Res Commun Mol Pathol Pharmacol. 1997 Nov Both modified or oxidized LDL and elevated LDL concentration are regarded as risks for atherosclerosis and ischemic heart disease, suggesting that higher body iron is important in this process.
In vitro studies of ferritin iron release and neurotoxicity J Neurochem 1998 Jun These results suggest that ferritin iron release contributes to free radical-induced cell damage in vivo.
Atherosclerosis, and Ischemic Heart Disease
Arch Intern Med. 1999; Objective To review the epidemiological and experimental data concerning iron and the development of atherosclerosis and ischemic heart disease.
Iron catalyzed oxidative damage, in spite of normal ferritin and transferrin saturation levels and its possible role in Werner's syndrome, Parkinson's disease, cancer, gout, rheumatoid arthritis, etc. Med Hypotheses 2000 Sep the disease is often overlooked by physicians, until several organs have been damaged permanently (heart, liver, brain, pancreas, kidneys, spleen, etc.). Moreover, since ferritin, transferrin saturation and hematocrit levels are not directly related to cellular iron levels, and since excess iron can wreak havoc in the cell, we can conclude that there is a need for a better way to evaluate intracellular iron levels and especially the intracellular free iron levels by a non-invasive technique.
Iron Imbalance in the Brain is a factor in Many Neurological Disorders James R. Connor, Ph.D. speaker at the International Patient Conference, Iron Disorders Institute October 2001
Loading and Disease Surveillance
Eugene D. Weinberg Indiana University, Bloomington, Indiana Emerging Infectious Diseases Journal, National Center for Infectious Diseases, Centers for Disease Control and Prevention. Excessive iron in specific tissues and cells (iron loading) promotes development of infection, neoplasia, cardiomyopathy, arthropathy, and various endocrine and possibly neurodegenerative disorders.
Iron overload and psychiatric illness Can J Psychiatry 1994 Feb, Dr. Paul Cutler. These cases indicate a need to be aware that disordered iron metabolism is a somatic cause of psychiatric illness and that there is clinical improvement upon lowering elevated iron levels in patients with iron overload.
overload, oxidative stress, and axonal dystrophy in brain disorders
Pediatr Neurol 2001 Aug
Iron overload without the C282Y mutation in patients with epilepsy. J Neurol Neurosurg Psychiatry. 2001 Apr; To test the hypothesis that iron overload predisposes to epilepsy, transferrin saturation in 130 patients with epilepsy and sex and age matched 128 control subjects without epilepsy were studied.
Problems May Lead to Parkinson's
Mouse study shows direct link. By Julia McNamee Neenan HealthScout Reporter 1-30-01
disorders shed light on Parkinson's
By Emma Hitt,PhD Health Talk with Dr. Bob Martin July 2001
Iron uptake by glial cells. The data reinforces the likelihood that iron uptake by nervous tissues is transferrin-mediated. Neurochem Res 1985 Dec.
Alzheimer's disease iron overload of the brain?
Alzheimer's Research Journal VOLUME: 03 ISSUE: 01 PAGES: 69-72
Is hemochromatosis a risk factor for Alzheimer’s disease? Journal of Alzheimer's Disease Volume 3, Number 5, October 2001 Pages 471-477 J. R.Connor, E. A. Milward, S. Moalem, M. Sampietro, P. Boyer, M. E.Percy, C. Vergani, R. J. Scott, M. Chorney (communicated by Paolo Zatta)
Is Parkinson's disease a progressive siderosis of substantia nigra resulting in iron and melanin induced neurodegeneration? Acta Neurol Scand Suppl 1989 Thus, without evoking environmental neurotoxins, the excessive accumulation of free iron in the SN and "melanin-trap" could be the trigger for accelerated cell death and Parkinsonism.
Parkinson's disease the heterozygote form of Wilson's disease: PD = 1/2 WD?
Med Hypotheses 2001 Feb
Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice. Proc Natl Acad Sci U S A. 2001 Jul 17 In conclusion, our results highlight the role of hepcidin as a key regulator of iron homeostasis. We propose hepcidin as a novel candidate gene that, when mutated, could be involved in abnormal regulation of iron metabolism and development of HH. Finally, this new murine model of iron overload disease appears to be a suitable animal model for testing new therapeutic approaches for prevention and correction of the iron storage in HH as well as for the understanding of iron homeostasis.
Low Molecular Weight Iron in Cerebral Ischemic Acidosis In Vivo Stroke 1998;29:487-493 AHA. This enlightening study constitutes a starting point for future investigations focusing on the effect of cerebral ischemia on the cellular and molecular factors regulating free intracellular iron.
Low penetrant hemochromatosis phenotype in eight families: no evidence of
modifiers in the mhc region.
Blood Cells Mol Dis. 2001 Mar-Apr We investigated eight families including C282Y homozygous relatives showing no clinical signs of the disease, in addition to the hemochromatosis patients.
evaluation of brain iron in earlier- and later-onset Parkinson's
Magn Reson Imaging 1999 Feb The FDRI results suggest that disregulation of iron metabolism occurs in PD and that this disregulation may differ in earlier- versus later-onset PD.
National Institute for Neurological Disorders and Stroke all mention iron involvement in the brain:
Narrative from the FY2001 Congressional Justification for Non-AIDS Activities
Parkinson's Disease: A Research Planning Workshop
Parkinson's Disease - Hope Through Research
NINDS Zellweger Syndrome Information Page
Disease as Multifactorial Oxidative Neurodegeneration:
Implications for Integrative Management Parris M. Kidd, PhD
Parkinson's Disease: A Research Planning Workshop National Institute of Neurological Disorders and Stroke Iron levels are high in the brain, and iron promotes reactions that create free radicals.
Parkinson's Disease as Multifactorial Oxidative Neurodegeneration: Implications for Integrative Management Alternative Medicine Review - Volume 5, Number 6, December 2000, Parris M. Kidd, PhD. The SN is uniquely vulnerable to oxidative damage, having a high content of oxidizable dopamine, neuromelanin, polyunsaturated fatty acids, and iron, and relatively low antioxidant complement with high metabolic rate.
Parkinson's Disease - Hope Through Research National Institute of Neurological Disorders and Stroke: Evidence that oxidative mechanisms may cause or contribute to Parkinson's disease includes the finding that patients with the disease have increased brain levels of iron, especially in the substantia nigra.
PULLING IRON OUT OF THE FIRE by Shelly Morrow. This article appeared in the Sept/Oct 2000 issue of Arthritis Today, published by the Arthritis Foundation, Inc.,
advances in disorders of iron metabolism: mutations, mechanisms and modifiers
Hum Mol Genet 2001 Oct 1
scientific advances in neurogenetics, Friedreich's Ataxia, iron & yeast
A brain imaging technique has shown that iron levels are indeed selectively elevated in the brains of patients with Friedreich's, suggesting that targeting iron metabolism may help treat the disease.
distribution of iron and iron-regulatory proteins in the brain in aging and
J Neurosci Res 1992 Feb The observations in this study are consistent with our general hypothesis that iron homeostasis is disrupted in the aging brain and the alterations in iron-regulatory proteins are exacerbated in Alzheimer's disease.
Regional distribution of iron, transferrin, ferritin, and oxidatively-modified proteins in young and aged Fischer 344 rat brains Neuroscience 1997 Jul Iron dysregulation in the brain is thought to contribute to the oxidative damage seen in neurodegenerative diseases including Alzheimer's disease and Parkinson's disease.
Regulation of Expression of Iron Binding Proteins in the Nervous System,
James R. Connor, Ph.D., University of California, Berkeley, 1981; Postdoctoral Training, Boston University School of Medicine, 1981-1983 The goal of this laboratory is to learn how the brain maintains an appropriate balance and ready supply of iron and what happens to normal brain function when an imbalance of iron occurs. Our research efforts are directed at the proteins which regulate iron bioavailability. Our data had led to the discovery that the brain's ability to mobilize iron is diminished in Alzheimer's Disease and in specific regions of the brain in Parkinson's Disease.
hemochromatosis From: Oct 1999 In Journals: Neurology
4 articles returned that require subscriptions
T1 and T2 in the brain of healthy subjects, patients with Parkinson disease, and patients with multiple system atrophy: relation to iron content Radiology. 1999; In conclusion, the results of this study confirm and extend earlier reports of the linear relation between MR signal and iron content in iron-containing deep nuclei. This study is more robust in that both T1 and T2 changes are used, providing a more specific and accurate determination of changes in iron content and form
The hemochromatosis gene affects the age of onset of sporadic Alzheimer's disease HFE mutations may anticipate AD clinical presentation in susceptible individuals. Neurobiol Aging 2001 Jul-Aug
The HFE CYS282Tyr
polymorphism is associated with cardiovascular mortality.
Roest M, Schouw Yvd, B. de Valk BD, Marx JJM, Tempelman M, de Groot P, Sixma J, Banga JD. Presented at the July 1998 meeting of the European Iron Club. Conclusions: Heterozygosity for HH is associated with increased risk of cerebrovascular and total cardiovascular mortality, in particular in combination with hypertension and smoking. Long term exposure to minimal iron overload may enhance atherosclerosis.
The possible role of iron in the etiopathology of Parkinson's disease Mov Disord 1993 The recently described pathology of PD supports the view for a state of oxidative stress in the substantia nigra (SN), resulting as a consequence of the selective accumulation of iron in SN zona compacta and within the melanized dopamine neurons.
role of iron in neurodegeneration: prospects for pharmacotherapy of Parkinson's
Drugs Aging 1999 Feb;Although the aetiology of Parkinson's disease (PD) and related neurodegenerative disorders is still unknown, recent evidence from human and experimental animal models suggests that a misregulation of iron metabolism, iron-induced oxidative stress and free radical formation are major pathogenic factors.
and iron in normal, Alzheimer's disease, and Parkinson's disease brain regions.
J Neurochem 1995 Aug Department of Medicine, Sinai Hospital, Detroit, MI. The altered relationship between iron and transferrin provides further evidence that a disturbance in iron metabolism may be involved in both disorders.
Transferrin C2 and Alzheimers Med Hypotheses 1995 Apr We hypothesize that Alzheimer's disease is caused by free radical damage to membranes of endocytic vesicles due to defective binding of iron and aluminium by Tf C2.
Zellweger Syndrome Information Page
National Institute of Neurological Disorders and Stroke The most common features of Zellweger syndrome include an enlarged liver, high levels of iron and copper in the blood, and vision disturbances.
Back to the "Munnsters" main Hemochromatosis page