J147 rescues cognitive deficits in aged Alzheimer's disease mice. huAPP/PS1 mice were aged to 20 months old. The mice were then put on the control food diet or 200 ppm J147 food diet (10 mg/kg/day). Following three months of treatment, all mice were analyzed for spatial memory by the two-day water maze, disinhibition phenotype by the elevated plus maze and hippocampal dependent memory by fear conditioning. (A) The two-day water maze analyzes spatial navigational memory. Visible V4 refers to visible platform trial 4 (Day 1), which is the last visible platform trial before testing and, therefore, represents the baseline. During testing on Day 2, the time it takes each mouse to find the hidden platform during trial 1 (hidden T1) is measured as escape latency. AD mice control (white boxes), took considerably longer to find the hidden platform than AD mice fed J147 (black boxes), suggesting that J147 improved the navigational memory of mice. (B) The elevated plus maze analyzes the anxiety response of mice by comparing the time spent on the open arms to time spent on the closed arms. AD alone mice (white box) spent more time in the open arms than AD mice fed J147 (black box) suggesting that J147 treatment reduced the disinhibition phenotype. (C and D) Fear conditioning to either a cue or a context represents a form of associative learning. The readout that is measured in contextual and cued fear conditioning is a freezing response that occurs following the pairing of an unconditioned stimulus such as a foot shock, with a conditioned stimulus such as a particular context or cue (tone). (C) AD mice on the J147 diet (black box) spent much more time freezing on Day 2, demonstrating a significant improvement in hippocampal related memory compared to AD mice on the control diet (white box). (D) There was no significant difference in freezing response on day three (cued memory) between AD control and AD mice on J147 diet. These results suggest that J147 improved the cognitive performance in AD mice. One-way ANOVA and Tukey post hoc test were used to determine the statistical significance of the behavioral responses, N = 11 AD Control, N = 12 AD + J147. *P <0.05, *** P <0.001.