Prevalent iron metabolism gene variants associated with increased brain ferritin iron in healthy older men

George Bartzokis, Po H. Lu, Todd A. Tishler, Douglas G. Peters, Anastasia Kosenko, Katherine A. Barrall, J. Paul Finn, Pablo Villablanca, Gerhard Laub, Lori L. Altshuler, Daniel H. Geschwind, Jim Mintz, Elizabeth Neely, James R. Connor

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Prevalent gene variants involved in iron metabolism [hemochromatosis (HFE) H63D and transferrin C2 (TfC2)] have been associated with higher risk and earlier age at onset of Alzheimer's disease (AD), especially in men. Brain iron increases with age, is higher in men, and is abnormally elevated in several neurodegenerative diseases, including AD and Parkinson's disease, where it has been reported to contribute to younger age at onset in men. The effects of the common genetic variants (HFE H63D and/or TfC2) on brain iron were studied across eight brain regions (caudate, putamen, globus pallidus, thalamus, hippocampus, white matter of frontal lobe, genu, and splenium of corpus callosum) in 66 healthy adults (35 men, 31 women) aged 55 to 76. The iron content of ferritin molecules (ferritin iron) in the brain was measured with MRI utilizing the Field Dependent Relaxation Rate Increase (FDRI) method. 47% of the sample carried neither genetic variant (IRON-) and 53% carried one and/or the other (IRON+). IRON+ men had significantly higher FDRI compared to IRON- men (p=0.013). This genotype effect was not observed in women who, as expected, had lower FDRI than men. This is the first published evidence that these highly prevalent genetic variants in iron metabolism genes can influence brain iron levels in men. Clinical phenomena such as differential gender-associated risks of developing neurodegenerative diseases and age at onset may be associated with interactions between iron genes and brain iron accumulation. Clarifying mechanisms of brain iron accumulation may help identify novel interventions for age-related neurodegenerative diseases.

Original languageEnglish (US)
Pages (from-to)333-341
Number of pages9
JournalJournal of Alzheimer's Disease
Volume20
Issue number1
DOIs
StatePublished - 2010

Keywords

  • Alpha synuclein
  • Lewy body
  • amyloid
  • basal ganglia
  • chelation
  • dementia
  • diet
  • free radicals
  • gene
  • gray matter
  • iron
  • metal
  • myelin
  • oligodendrocytes
  • prevention
  • risk
  • tau
  • treatment

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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  • Cite this

    Bartzokis, G., Lu, P. H., Tishler, T. A., Peters, D. G., Kosenko, A., Barrall, K. A., Finn, J. P., Villablanca, P., Laub, G., Altshuler, L. L., Geschwind, D. H., Mintz, J., Neely, E., & Connor, J. R. (2010). Prevalent iron metabolism gene variants associated with increased brain ferritin iron in healthy older men. Journal of Alzheimer's Disease, 20(1), 333-341. https://doi.org/10.3233/JAD-2010-1368