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

被引:288
作者
Bartzokis, George
Tishler, Todd A.
Lu, Po H.
Villablanca, Pablo
Altshuler, Lori L.
Carter, Michele
Huang, Danny
Edwards, Nancy
Mintz, Jim
机构
[1] Univ Calif Los Angeles, Alzheimers Dis Res Ctr, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA
[3] Univ Calif Los Angeles, David Geffen Sch Med, Lab Neuroimaging, Dept Neurol,Div Brain Mapping, Los Angeles, CA 90095 USA
[4] Greater Los Angeles VA Healthcare Syst, Dept Psychiat, Los Angeles, CA 90073 USA
[5] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA
[6] Univ Calif Los Angeles, David Geffen Sch Med, Neurosci Interdept Grad Program, Los Angeles, CA 90095 USA
[7] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol, Los Angeles, CA 90095 USA
关键词
brain; iron; ferritin; MRI; FDRI; gender; sex; dementia; risk; age; onset; neurodegeneration; hemochromatosis; free radicals; treatment; prevention; myelin; white matter; oligodendrocytes; hippocampus; frontal lobe; protemopathy;
D O I
10.1016/j.neurobiolaging.2006.02.005
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
Background: Brain iron promotes oxidative damage and protein oligornerization 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. (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码:414 / 423
页数:10
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