A, B, Quantification of hilar GABAergic interneurons positive for GAD67 in female (A) or male (B) apoE-KI mice at 1, 3, 6, 12, and 16 months of age (n = 6−12 mice per group). Results in histograms are presented as the total number of positive cells counted per brain. Female apoE-KI mice show an apoE isoform-dependent and age-dependent effect, but no interaction between the two variables was observed by 2-way ANOVA [28]. *p<0.05; **p<0.01 in female apoE4-KI mice compared to female apoE3-KI mice at the same age (post-hoc Bonferroni test). Male apoE-KI mice also show an apoE isoform–dependent effect, and further exhibit an interaction between the two variables by 2-way ANOVA, *p<0.05 (post-hoc Bonferroni test). C, D, Quantification of GAD67-positive hilar interneurons in female and male apoE3-KI (C) or apoE4-KI (D) mice at 1, 3, 6, 12, and 16 months of age (n = 6−12 mice per group). ApoE3-KI mice show a sex-dependent effect, with interaction between sex and age by 2-way ANOVA. ApoE4-KI mice show an age-dependent, but sex-independent, effect with interaction between the two variables by 2-way ANOVA. *p<0.05; **p<0.01; ***p<0.001 in male apoE-KI mice compared to their female counterparts (post-hoc Bonferroni test). E–H, Representative images (200x) of anti-GAD67-immunostained sections of the hilus of female apoE3-KI (E), female apoE4-KI (F), male apoE3-KI (G), and male apoE4-KI (H) mice at 16 months of age. I, J, Escape latency in hidden platform days 1−5 correlated inversely with the number of GAD67-positive hilar interneurons in female apoE4-KI mice (J, n = 12) but not female apoE3-KI mice (I, n = 10) at 16 months of age [28].