Brain Iron Deposition And Cognitive Dysfunction In Adult Wild-type Mice And APP/PS1 Transgenic Mice Are Independent Of Dietary Iron Content

Brain iron deposition is one of the features of Alzheimer’s disease(AD)and may contribute to its development.However,the relative contribution of dietary iron remains unclear.The aim of this study is to compare the impact of high dietary iron on pathological changes in the brain and cognitive function in adult wild-type(WT)mice and APP/PS1 double transgenic mice,a mouse model of AD.WT mice and APP/PS1 mice at 10 wk of age were fed either a control diet or a high iron diet(14 g Fe/kg)for 20 wk.We found that feeding mice a high iron diet did not significantly affect brain iron concentrations.In contrast,in the APP/PS1 genetic model of AD,the iron concentration in the hippocampus was significantly higher(2-3 fold)than that of WT mice when the animals were on diets with either a normal or high iron content.Histological analysis indicated that iron accumulated in the hippocampal dentate gyrus region in APP/PS1 mice,consistent with the pattern of amyloid-β(Aβ)deposition.In WT mice on a high iron diet,however,Aβ was diffusely distributed.Furthermore,superoxide dismutase(SOD)activity and malondialdehyde(MDA)concentration were tested to determine the oxidative stress in mouse hippocampus,and cognitive functions were tested with the Morris water maze system.We found that iron treatment had little impact on oxidative stress and cognitive function,despite its stimulating effect on Aβ and phospho-tau expression in the hippocampus.In APP/PS1 mice,however,oxdative stress was significantly higher in the hippocampus than in WT mice,and cognitive dysfunction was apparent.In conclusion,dietary iron overload contributes little to brain iron accumulation and cognitive dysfunction in adult mice.