Abstract
Previous studies have shown that the APP/PS1, double transgenic mouse model of Alzheimer's disease (AD), develops cognitive dysfunction and Abeta deposits from 5 to 6 months of age. We exposed 1 month old APP/PS1 mice to dietary folate deficiency (FD) for 5 months to test the hypothesis that long term FD accelerates AD‐related pathology and thus contributes to cognitive dysfunction. Results showed a robust disruption in learning and memory performance assessed by the novel object recognition (NOR) test in FD group suggesting abnormalities in the cortex of FD mice. NOR behavior was negatively correlated with the plaque burden in the cortex (r=−.55; P<0.05) but not in the hippocampus (r=−.38; P=.20). The size of the plaques was also significantly larger in the cortex of FD mice as compared to those in the control group; and it was negatively correlated with the cortical choline‐containing lipids (r=−.48; P<.05). There was 30% decrease in the concentration of sphingomyelin in the cortex of FD mice but not in the hippocampus. Our findings suggest a higher sensitivity of the cortex to long term FD and AD related pathology as compared to the hippocampus of APP/PS1 mice.