Onset of radial-arm water maze deficit occurs between 16 and 18 months for outcrossed AβPP/PS1 mice and as early as 8 months in inbred C57BL/6 AβPP/PS1 mice. (A) Diagram of radial-arm water maze. Maze contained six arms with large visual cues positioned on the walls of the room adjacent to the distal end of each arm. A hidden platform (HP) was submerged at the end of one arm. (B) Controls assessing escape motivation, swimming ability, and vision across trials in outcrossed WT and AβPP/PS1 mice at 12, 16, and 18 months and inbred C57BL/6 WT and AβPP/PS1 mice at 8 months. Symbols represent mean seconds per excursion during first five trials ± SE. Two-factor ANOVAs (genotype × group): no interaction, F < 1. Errors made across trials by WT and AβPP/PS1 mice at (C-E) 12, 16, and 18 months in outcrossed mice and (F) 8 months in inbred C57BL/6 mice. Symbols represent mean errors made per trial during groups of five trials ± SE. Two-factor ANOVAs (genotype × trial) with repeated measures (trial): 12 months outcrossed: main effect of trial, F(5,27) = 22.08, p < 0.001; 16 months outcrossed: main effect of trial, F(5,10) = 15.63, p < 0.001; 18 months outcrossed: interaction, F(5,14) = 4.35, p < 0.01; 8 months inbred C57BL/6: interaction, F(5,19) = 4.63, p < 0.001. Post hoc Student’s t-tests, *p < 0.05, ***p < 0.001. Excursion time and water maze analyses: 12 months outcrossed: WT, n = 15 mice; AβPP/PS1, n = 14 mice; 16 months outcrossed: WT, n = 5 mice; AβPP/PS1, n = 7 mice; 18 months outcrossed: WT, n= 8 mice; AβPP/PS1, n = 8 mice; 8 months inbred C57BL/6: WT, n = 11 mice; AβPP/PS1, n = 10 mice. (G-H) Performance in radial-arm water maze reversal does not differ between WT and AβPP/PS1 mice at 12 months. (G) Total errors and (H) perseverant errors made per trial by WT and AβPP/PS1 mice during reversal task at 12 months. Symbols represent mean errors made per trial during groups of four trials ± SE. Two-factor ANOVAs (genotype × trial) with repeated measures (trial): total errors: main effect of trial, F(2,27) = 29.36, p < 0.001; perseverant errors: main effect of trial, F(2,27) = 15.09, p < 0.001. Water maze reversal analyses: 12 months: WT, n = 15 mice; AβPP/PS1, n = 14 mice.