Brain ferritin iron may influence age- and gender-related risks of neurodegeneration

George Bartzokis, Todd A. Tishler, Po H. Lu, Pablo Villablanca, Lori L. Altshuler, Michele Carter, Danny Huang, Nancy Edwards, Jim Mintz

Research output: Contribution to journalArticle

234 Scopus citations

Abstract

Background: Brain iron promotes oxidative damage and protein oligomerization that result in highly prevalent age-related proteinopathies such as Alzheimer's disease (AD), Parkinson's disease (PD), and Dementia with Lewy Bodies (DLB). Men are more likely to develop such diseases at earlier ages than women but brain iron levels increase with age in both genders. We hypothesized that brain iron may influence both the age- and gender-related risks of developing these diseases. Methods: The amount of iron in ferritin molecules (ferritin iron) was measured in vivo with MRI by utilizing the field dependent relaxation rate increase (FDRI) method. Ferritin iron was measured in four subcortical nuclei [caudate (C), putamen (P), globus pallidus (G), thalamus (T)], three white matter regions [frontal lobe (Fwm), genu and splenium of the corpus callosum (Gwm, Swm)] and hippocampus (Hipp) in 165 healthy adults aged 19-82. Results: There was a high correlation (r > 0.99) between published post-mortem brain iron levels and FDRI. There were significant age-related changes in ferritin iron (increases in Hipp, C, P, G, and decreases in Fwm). Women had significantly lower ferritin iron than men in five regions (C, T, Fwm, Gwm, Swm). Conclusions: This is the first demonstration of gender differences in brain ferritin iron levels. It is possible that brain iron accumulation is a risk factor that can be modified. MRI provides the opportunity to assess brain iron levels in vivo and may be useful in targeting individuals or groups for preventive therapeutic interventions.

Original languageEnglish (US)
Pages (from-to)414-423
Number of pages10
JournalNeurobiology of Aging
Volume28
Issue number3
DOIs
StatePublished - Mar 1 2007

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Keywords

  • Age
  • Brain
  • Dementia
  • FDRI
  • Ferritin
  • Free radicals
  • Frontal lobe
  • Gender
  • Hemochromatosis
  • Hippocampus
  • Iron
  • MRI
  • Myelin
  • Neurodegeneration
  • Oligodendrocytes
  • Onset
  • Prevention
  • Proteinopathy
  • Risk
  • Sex
  • Treatment
  • White matter

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

Bartzokis, G., Tishler, T. A., Lu, P. H., Villablanca, P., Altshuler, L. L., Carter, M., Huang, D., Edwards, N., & Mintz, J. (2007). Brain ferritin iron may influence age- and gender-related risks of neurodegeneration. Neurobiology of Aging, 28(3), 414-423. https://doi.org/10.1016/j.neurobiolaging.2006.02.005