Brain ferritin iron may influence age- and gender-related risks of neurodegeneration.
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.
Bartzokis
George
G
Department of Neurology, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA. gbar@ucla.edu <gbar@ucla.edu>
Tishler
Todd A
TA
Lu
Po H
PH
Villablanca
Pablo
P
Altshuler
Lori L
LL
Carter
Michele
M
Huang
Danny
D
Edwards
Nancy
N
Mintz
Jim
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D001921:Brain / Q000378:metabolism*; D005260:Female; D005293:Ferritins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D007501:Iron / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000473:pathology*; D011180:Postmortem Changes; D012727:Sex Characteristics
D005293:Ferritins; D007501:Iron