Review Article
Volume 12 Issue 1 - 2020
Iron Deposition in the Brain during the Aging Process and in Neurodegenerative Diseases: A Post-Mortem Review Study
Jacques L De Reuck*
Unitè 1171 “Degenerative and Vascular Cognitive Disorders”, Université de Lille 2, Lille, France
*Corresponding Author:Jacques L De Reuck, Unitè 1171 “Degenerative and Vascular Cognitive Disorders”, Université de Lille 2, Lille, France.
Received: November 20, 2019; Published: December 30, 2019


Background and Purpose: The role of iron (Fe) accumulation in the brain is still a matter of debate. The present review examines all the available post-mortem data in the aging brain and in those with neurodegenerative diseases. 

Results: During normal aging there is a progressive increase of Fe, mainly in the basal ganglia. Most neurodegenerative diseases display Fe accumulation during the progression of their disorder. This is the most severe in frontotemporal lobar degeneration and to a lesser degree in amyotrophic lateral sclerosis and Parkinson’s disease. 

Conclusion: In all neurodegenerative diseases and during aging there is evidence that Fe accumulation contributes to further neuronal degeneration and promotes disease progression.

Keywords: Post-Mortem Brain Iron; Normal Aging; Alzheimer’s Disease; Frontotemporal Lobar Degeneration; Lewy Body Disease; Parkinson’s Disease; Progressive Supranuclear Palsy; Amyotrophic Lateral Sclerosis; Multiple System Atrophy


  1. Morris G., et al. “Why should neuroscientists worry about iron? The emerging role of ferroptosis in the pathophysiology of neuroprogressive diseases”. Behavior Brain Research 314 (2018): 154-175. 
  2. van Duijn S., et al. “Histological techniques to visualize iron in paraffin embedded brain tissue of patients with Alzheimer’s disease”. Journal of Histochemistry and Cytochemistry 61 (2013): 785-792.
  3. Duflou H., et al. “Regional distribution of potassium, calcium and trace elements in normal human brain”. Neurochemistry Research 14 (1989): 1099-1112.
  4. Duflou H., et al. “Application of PIXE analysis to the study of the regional distribution of trace elements in normal human brain”. Biologic Trace Element Research 13 (1987): 1-17.
  5. De Reuck j., et al. “Age-related iron deposition in the deep brain structures of normal subjects: a post-mortem 7.0-tesla study magnetic resonance study”. Acta Scientific Neurology 2 (2019): 2-5.
  6. De Reuck J., et al. “Comparison of 7.0 T T2*- magnetic resonance imaging of cerebral bleeds in post-mortem brain sections of Alzheimer patients with neuropathological correlates”. Cerebrovascular Diseases 31 (2011): 511-517.        
  7. Gupta D., et al. “Utility of susceptibility-weighted MRI in differentiating Parkinson’s disease and atypical parkinsonism”. Neuroradiology 52 (2010): 1087-1094.
  8. Costagli M., et al. “Magnetic susceptibility in the deep layers of the primary motor cortex in amyotrophic lateral sclerosis”. Neuroimage Clinical 12 (2016): 965-969.
  9. Dringen R., et al. “The pivotal role of astrocytes in the metabolism of iron in the brain”. Neurochemistry Research 32 (2007): 1884-1890.
  10. Langkammer C., et al. “Quantitative MR imaging of brain iron: a postmortem validation study”. Radiology 257 (2010): 455-462. 
  11. Hebbrecht G., et al. “Brain trace elements and aging”. Nuclear Instrument Method Physiology Research150 (1999): 208-213.
  12. Daugherty A and Raz N. “Age-related differences in iron content of subcortical nuclei observed in vivo: a meta-analysis”. Neuroimage 70 (2013): 113-121.
  13. Zecca L., et al. “Iron, neuromelanin and ferritin content in the substantia nigra of normal subjects at different ages: consequences for iron storage and neurodegenerative processes”. Journal of Neurochemistry 76 (2001): 1766-1773.
  14. Markesbery WR., et al. “Brain trace element concentration in aging”. Neurobiological Aging 5 (1984): 19-28.
  15. Grolez G., et al. “The value of magnetic resonance imaging as biomarker of amyotrophic lateral sclerosis: a systematic review”. BMC Neurology. 16 (2016): 155.
  16. Wiethoff S and Houlden H. “Neurodegeneration with brain iron accumulation”. Handbook of Clinical Neurology 145 (2017): 157-166.
  17. Ward RJ., et al. “The role of iron in brain ageing and neurodegenerative disorders”. Lancet Neurology 13 (2014): 1045-1060.
  18. Jellinger K., et al. “Brain iron and ferritin in Parkinson’s and Alzheimer’s diseases”. Journal of Neural Transmission. Parkinson's Disease and Dementia Section 2 (1990): 327-340.
  19. Gerlach M., et al. “Altered brain metabolism of iron as a cause of neurodegenerative diseases”. Journal of Neurochemistry 6 (1994): 793-807.
  20. Schipper HM. “Glial HO-1 expressions, iron deposition and oxidative stress in neurodegenerative disease”. Neurotoxicology Research 1 (1999): 57-70. 
  21. Schmidt LM and Gotzsche PC. “Of mites and men: reference bias in narrative review articles: A systemic review”. Journal of Family Practice 54 (2006): 334-338.
  22. Hare DJ., et al. “Laser ablation inductively coupled plasma-mass spectroscopy imaging of white and gray matter iron distribution in Alzheimer’s disease frontal cortex”. Neuroimage 137 (2016): 124-131.
  23. Schrag M., et al. “Iron, zinc and copper in the Alzheimer’s disease brain; a quantitative meta-analysis. Some insight on the influence on citation opinion”. Progress in Neurobiology 94 (2011): 296-306.
  24. Schragh M., et al. “Iron, zinc and copper in Alzheimer’s disease”. Journal of Alzheimers Disease 24 (2011): 137-149.
  25. De Reuck J., et al. “Iron deposits in post- mortem brains of patients with neurodegenerative and cerebrovascular diseases: a semi-quantitative 7.0 T magnetic resonance imaging study”. European Journal of Neurology 21 (2014): 1026-1031.
  26. Sieben A., et al. “The genetic and neuropathology of frontotemporal lobar degeneration”. Acta Neuropathologica 124 (2012): 353-372.
  27. Ehmann WD., et al. “Brain trace elements in Pick’s disease”. Annales of Neurolology 15 (1984): 102-104.
  28. Veyrat-Durebex C., et al. “Iron metabolism disturbance in a French cohort of ALS patients”. Biomedical Research International. 10 (2014). 
  29. Kasarskis EJ., et al. “Aluminium, calcium, and iron in the spinal cord of patients with sporadic amyotrophic lateralsclerosis using laser micropro be mass spectroscopy: a preliminary study”. Journal of Neurological Sciences 130 (1995): 203-208.
  30. Hecht MJ., et al. “Cortical T2 signal shortening in amyotrophic lateral sclerosis is not due to iron deposits”. Neuroradiology 47 (2005): 805-808.
  31. Igjatovic A., et al. “Brain iron MRI: a biomarker for amyotrophic lateral sclerosis”. Journal of Magnetic Resonance Imaging 38 (2013): 1472-1479.
  32. De Reuck J., et al. “Topographic distribution of brain iron deposition and small cerebrovascular lesions in amyotrophic lateral sclerosis and in frontotemporal lobar degeneration: a post-mortem 7.0-tesla magnetic resonance imaging study with neuropathological correlates”. Acta Neurologica Belgica 117 (2017): 873-878.
  33. Kioumourtzoglou MA., et al. “Diabetes, obesity, and diagnosis of amyotrophic lateral sclerosis: a populationbased study”. JAMA 72 (2015): 905-911. 
  34. Santillo AF., et al. “Frontotemporal dementia- amyotrophic lateral sclerosis complex is simulated by neurodegeneration with brain iron accumulation”. Alzheimer Disease and Associated Disorders 23 (2009): 298-300.
  35. Prpar Mihevc S., et al. “Nuclear trafficking in amyotrophic lateral sclerosis and frontotemporal lobar degeneration”. Brain 140 (2017): 13-26.
  36. Riku Y., et al. “Lower motor involvement in TAR DNA-binding protein of 43 kDa related frontotemporal lobar degeneration and amyotrophic lateral sclerosis”. JAMA Neurolology71 (2014): 172-179. 
  37. Riederer P., et al. “Transition metals, ferritin, gluthione, and ascorbic acid in parkinsonian brains”. Journal of Neurochemistry 52 (1989): 515-520. 
  38. Kitao S., et al. “Correlation between pathology and neuromelanin MR imaging in Parkinson’s disease and dementia with Lewy bodies”. Neuroradiology 55 (2013): 947-953. 
  39. Guan X., et al. “Regionally progressive accumulation of iron in Parkinson’s disease as measured by quantitative susceptibility mapping”. NMR in Biomedicine 30 (2017).
  40. Ivothi HJ., et al. “Aging causes morphological alterations in astrocytes and microglia in human substantia nigra pars compacta”. Neurobiology of Aging 36 (2015): 3321-3333.
  41. Gu M., et al. “Mitochondrial function, GSH and iron in neurodegeneration and Lewy body disease”. Journal of Neurological Sciences 158 (1998): 24-29.
  42. Kitao S., et al. “Correlation between pathology and neuromelanin MR imaging in Parkinson’s disease and dementia with Lewy bodies”. Neuroradiology 55 (2013): 947-953. 
  43. Foroutan P., et al. “Progressive supranuclear palsy: high-field-strength MR microscopy in the human substantia nigra and globus pallidus”. Radiology 266 (2013): 280-288. 
  44. Lee SH, et al. “Brain regional iron contents in progressive supranuclear palsy”. Parkinsonism Related Disorders 45 (2017): 28-32. 
  45. De Reuck J., et al. “Prevalence of small cerebral bleeds in patients with progressive supranuclear palsy: a neuropathological study with 7.0- Tesla magnetic resonance imaging correlates”. Folia Neuropathologica 52 (2014): 421-427.
  46. Han YH., et al. “Topographic differences of brain iron deposition between progressive supranuclear palsy and parkinsonian variant multiple system atrophy”. Journal of Neurological Sciences 325 (2013): 29-35.
  47. Lee JH., et al. “Quantitative assessment of subcortical atrophy and iron content in progressive supranuclear palsy and parkinsonian variant of multiple system atrophy”. Journal of Neurology 260 (2013): 2094-2101. 
  48. Sugiyama A., et al. “Putaminal hypointensity on T2*- weighted MR imaging is the most practically useful sign in diagnosing multiple system atrophy: A preliminary study”. Journal of Neurological Sciences 349 (2015): 174-178.
  49. Van den Bogaard SJ., et al. “The role of iron imaging in Huntington disease”. International Review of Neurobiology 110 (2013): 241-250.
  50. Dominguez JF., et al. “Iron accumulation in the basal ganglia in Huntington’s disease: cross-sectional data from the IMAGE- HD study”. Journal of Neurology, Neurosurgery and Psychiatry 87 (2016): 545-549.
  51. Litwin T., et al. “Brain metal accumulation in Wilson’s disease”. Journal of Neurological Sciences 329 (2013): 55-58.
  52. Skowronska M., et al. “Does brain degeneration in Wilson disease involve not only copper but also iron accumulation?” Neurologia I Neurochirurgia Polska 47 (2013): 542-546.
  53. Dusek P., et al. “Brain iron accumulation in Wilson’s disease”. Neuropathology and Applied Neurobiolology 43 (2017): 514-532.
  54. De Reuck J. “Iron deposition in cerebrovascular diseases: a post-mortem review”. International Journal of Neurology and Psychiatry 1 (2019): 1001-1006.
  55. Bergsland N., et al. “White matter tract injury is associated with deep gray matter iron deposition in multiple sclerosis”. Neuroimaging 27 (2017): 107-113.
  56. Popescu BF., et al. “Pathogenic implications of distinct patters of iron and zinc in chronic MS lesions”. Acta Neuropathologica 134 (2017): 45- 64.
  57. Daglas M and Adlard PA. “The involvement of iron in traumatic brain injury and neurodegenerative disease”. Frontiers in Neuroscience 12 (2018).  
  58. Schroder N., et al. “Role of brain iron accumulation in cognitive dysfunction: evidence from animal models and human studies”. Journal of Alzheimers Disease 34 (2013): 797-812.
  59. Hagemeier J., et al. “Brain iron accumulation in aging and neurodegenerative disorders”. Expert Review of Neurotherapeutics 12 (2012): 1467-1480.
  60. De Reuck J., et al. “Cerebrovascular lesions in cerebral amyloid angiopathy with and without Alzheimer’s disease: a neuropathological study with post-mortem 7.0-tesla magnetic resonance imaging”. EC Neurology 11 (2018): 954-960. 
  61. Ayton S., et al. “Alzheimer’s disease neuroimaging initiative. Evidence that iron accelerates Alzheimer’s pathology: a CSF biomarker study”. Journal of Neurology, Neurosurgery and Psychiatry 89 (2018): 456-460.
  62. Amit T., et al. “Targeting multiple Alzheimer’s disease etiologies with multimodal neuroprotective and neurorestorative iron chelators”. FASEB Journal 22 (2008): 1296-1305.
  63. Zucca FA., et al. “Interaction of iron, dopamine and neuromelanin pathways in brain aging and Parkinson’s disease”. Progress in Neurobiology 155 (2017): 96-119.
  64. Jiang H., et al. “Brain iron metabolism dysfunction in Parkinson’ disease”. Molecular Neurobiology 54 (2017): 3078-3101.
  65. Josephs KA., et al. “Anatomical correlates of stereotypes in frontotemporal lobar degeneration”. Neurobiology of Aging 29 (2008): 1859-1863.
  66. Leh SE., et al. “Fronto-striatal connections in the human brain: a probabilistic diffusion tractography study”. Neuroscience Letters 419 (2007): 113-118. 
  67. Gazzina S., et al. “Iron in frontotemporal lobar degeneration. A new subcortical pathological pathway?” Neurodegenerative Diseases 16 (2016): 172-178.
  68. Hider RC., et al. “The potential application of iron chelators for treatment of neurodegenerative diseases”. Metallomics 3 (2011): 239-249.
Citation: Jacques L De Reuck. “Iron Deposition in the Brain during the Aging Process and in Neurodegenerative Diseases: A Post-Mortem Review Study”. EC Neurology 12.1 (2020): 01-09.

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