Affiliations: [a] Department of Psychiatry and Biobehavioral Sciences, The David Geffen School of Medicine at UCLA, Los Angeles, CA, USA | [b] Department of Neurology, The David Geffen School of Medicine at UCLA, Los Angeles, CA, USA | [c] Laboratory of Neuroimaging, Department of Neurology, Division of Brain Mapping, UCLA, Los Angeles, CA, USA | [d] Greater Los Angeles VA Healthcare System, Department of Psychiatry, West Los Angeles, CA, USA
Correspondence:
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Correspondence to: George Bartzokis, M.D., 300 UCLA Medical Plaza, Suite 2200, Los Angeles, CA 90095-6968, USA. Tel.: +1 310 206 3207; E-mail: gbar@ucla.edu.
Abstract: Background:Iron can catalyze damaging free radical reactions. With age, iron accumulates in brain gray matter regions and may contribute to the risk of developing age-related diseases such as Alzheimer’s disease (AD). Prior MRI studies demonstrated increased iron deposits in basal ganglia regions; however, the hippocampus (Hipp), which is heavily damaged in AD, and comparator regions that are resistant to AD damage, such as thalamus (Th), have rarely been examined. Objective:To assess iron levels and evidence of tissue damage in Hipp and Th of AD subjects and healthy controls. Methods:Thirty-one AD and sixty-eight healthy control subjects participated in this study. High- and low-field strength MRI instruments were used in combination to quantify iron content of ferritin molecules (ferritin iron) using the field dependent relaxation rate increase (FDRI) method. Decreased transverse relaxation rate (R2) was used as an index of tissue damage. Results:Compared with healthy controls, AD subjects had increased ferritin iron in Hipp (p = 0.019) but not Th (p = 0.637), and significantly decreased R2 in Hipp (p < 0.001) but not Th (p = 0.37). In the entire sample, FDRI and R2 were negatively correlated. Conclusion:The data shows that in AD, Hipp damage occurs in conjunction with ferritin iron accumulation. Prospective studies are needed to evaluate how increasing iron levels may influence the trajectory of tissue damage and cognitive and pathologic manifestations of AD.
Keywords: Alzheimer's disease, chelation, dementia, ferritin, field dependent relaxation rate increase (FDRI), iron, magnetic resonance imagining (MRI), myelin, prevention, treatment
