Female 3xTg-AD mice perform more poorly than males on spontaneous alternation behavior (SAB), a hippocampal-dependent working memory task. (A) SAB performance did not decline with age or significantly differ by sex in non-transgenic C57Bl6/129S (WT) mice. (B) We observed an age-related decline in SAB performance in both females (solid bars) [F (3,20) = 0.87, p = 0.002] and males (open bars) [F (3, 7) = 0.67, p = 0.031]. This effect is significantly different between females and males in the 12–14 mo age group [F (3,19) = 6.58, p = 0.0001]. * p < 0.05 from males of same age group. (C) As a control for activity level, the number of arm entries was measured; it was not significantly different across groups [F (3,19) = 0.79, p = 0.56]. Data show mean values ± SEM.