Age-dependent significant decrease in numbers of GABAergic interneurons in the hilus of the dentate gyrus of female apoE4-KI mice. A–D, Representative photomicrographs (200×) from female apoE3-KI and apoE4-KI mice at 16 months of age show GABAergic interneurons in the hilus after staining with anti-GAD67 (A, B) and anti-somatostatin (C, D). E, F, Hilar GABAergic interneurons positive for GAD67 (E) or somatostatin (F) in female apoE3-KI and apoE4-KI mice at 1, 3, 6, 12, 16, and 21 months of age (n = 4–12 mice per group) were quantified as described in Materials and Methods. Values are mean ± SEM. *p < 0.05; **p < 0.01 versus apoE3-KI mice at the same age (t test). G, H, Representative photomicrographs (200×) show GABAergic interneurons in CA1 region of the hippocampus after staining with anti-GAD67. I, Quantification of GAD67-positive GABAergic interneurons in CA1 region of the hippocampus in 16-month-old female apoE3-KI (n = 10) and apoE4-KI (n = 12) mice. Values are mean ± SEM. J, K, Representative photomicrographs (200×) from female wild-type mice at 16 months of age show GABAergic interneurons in the hilus after staining with anti-GAD67 (J) and anti-somatostatin (K). L, M, Hilar GABAergic interneurons positive for GAD67 (L) or somatostatin (M) in female wild-type, apoE3-KI, and apoE4-KI mice at 3, 12, and 16 months of age (n = 6–12 mice per group) were quantified as described in Materials and Methods. Values are mean ± SEM. *p < 0.05; **p < 0.01 versus wild-type and apoE3-KI mice at the same age (t test).