Ethanol exposure dysregulates diurnal feeding behavior and peripheral metabolism in APP/PS1 mice. a) Decreased weekly food consumption in APP/PS1 with or without ethanol treatment during experimental weeks 6–9. b) Ethanol-treated APP/PS1 mice showed decreased food consumption during the dark period. Two-way ANOVA revealed trend of differences between drinking group (p = 0.0580) and genotype × drinking group (p = 0.0697). c) Ethanol-treated APP/PS1 mice showed increased food consumption during light cycle. 2-way ANOVA revealed significant genotype (p = 0.0107) and genotype × drinking group (p = 0.0009) effects. d) H2O-treated APP/PS1 mice showed lower fasted blood glucose concentrations prior to glucose tolerance test. 2-way ANOVA revealed significant genotype effect (p = 0.0273). e) Ethanol-treated APP/PS1 mice displayed glucose intolerance during glucose tolerance test. Two-way ANOVA revealed significance over time (p < 0.0109), and time × group (p < 0.0001). Tukey’s multiple comparisons revealed that EtOH-treated APP/PS1 mice had significantly higher blood glucose concentrations at 30-, 45-, and 60-min post-glucose injection. f) H2O- and EtOH-treated APP/PS1 mice had higher plasma glucose at the terminal timepoint. 2-way ANOVA revealed genotype effect (p = 0.0001). g) H2O-treated APP/PS1 mice had higher plasma lactate levels at the terminal time point compared to H2O-treated wildtype mice. 2-way ANOVA revealed a genotype effect (p = 0.0049). h) H2O- and EtOH-exposed APP/PS1 mice had decreased fed insulin levels at the terminal timepoint, compared to H2O-treated wildtype mice. 2-way ANOVA revealed a genotype effect (p = 0.0123). i) Calculated HOMA-IR values showed a trend trended towards decreased in H2O- and ethanol-exposed APP/PS1 mice. 2-way ANOVA revealed a genotype effect (p = 0.0381). Wildtype + H2O, n = 10; APP/PS1 + H2O, n = 9; Wildtype + EtOH, n = 7; APP/PS1 + EtOH, n = 8. *p < 0.05, **p < 0.01, ***p < 0.001.