Brain Ferritin Iron as a Risk Factor for Age at Onset in Neurodegenerative Diseases

Authors

  • GEORGE BARTZOKIS,

    Corresponding author
    1. Department of Neurology, UCLA, Los Angeles, California, USA
    2. Laboratory of Neuroimaging, Department of Neurology, Division of Brain Mapping, UCLA, Los Angeles, California, USA
    3. Greater Los Angeles VA Healthcare System, Department of Psychiatry, West Los Angeles, California, USA
    4. Department of Psychiatry, Charles R. Drew University of Medicine and Science, Los Angeles, California, USA
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  • TODD A. TISHLER,

    1. Greater Los Angeles VA Healthcare System, Department of Psychiatry, West Los Angeles, California, USA
    2. Neuroscience Interdepartmental Graduate Program, UCLA, Los Angeles, California, USA
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  • IL-SEON SHIN,

    1. Department of Neurology, UCLA, Los Angeles, California, USA
    2. Department of Psychiatry, Chonnam National University Medical School, Kwangju, Korea
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  • PO H. LU,

    1. Department of Neurology, UCLA, Los Angeles, California, USA
    2. Department of Psychiatry and Biobehavioral Sciences, UCLA, Los Angeles, California, USA
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  • JEFFREY L. CUMMINGS

    1. Department of Neurology, UCLA, Los Angeles, California, USA
    2. Department of Psychiatry and Biobehavioral Sciences, UCLA, Los Angeles, California, USA
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Address for correspondence: George Bartzokis, M.D., UCLA Alzheimer's Disease Center, 710 Westwood Plaza, Room 2-238, Los Angeles, CA 90095-1769. Fax: 310-268-3266. gbar@ucla.edu

Abstract

Abstract: Tissue iron can promote oxidative damage. Brain iron increases with age and is abnormally elevated early in the disease process in several neurodegenerative disorders, including Alzheimer's disease (AD) and Parkinson's disease (PD). Higher iron levels in males may contribute to higher risk for younger-onset PD and recent studies have linked the presence of the hemochromatosis gene with a younger age at onset of AD. We examined whether age at onset of PD and AD was associated with increased brain ferritin iron. Ferritin iron can be measured with specificity in vivo with MRI utilizing the field-dependent relaxation rate increase (FDRI) method. FDRI was assessed in three basal ganglia regions (caudate, putamen, and globus pallidus) and frontal lobe white matter for younger- and older-onset male PD and AD patients and healthy controls. Significant increases in basal ganglia FDRI levels were observed in the younger-onset groups of both diseases compared to their respective control groups, but were absent in the older-onset patients. The results support the suggestion that elevated ferritin iron and its associated toxicity is a risk factor for age at onset of neurodegenerative diseases such as AD and PD. Clinical phenomena such as gender-associated risk of developing neurodegenerative diseases and the age at onset of such diseases may be associated with brain iron levels. In vivo MRI can measure and track brain ferritin iron levels and provides an opportunity to design therapeutic interventions that target high-risk populations early in the course of illness, possibly even before symptoms appear.

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