A–D , Levels of soluble ( A , B ) and insoluble ( C , D ) Aβ in hippocampal homogenates from PDAPP mice expressing human apolipoprotein E alleles at different ages. A , ^& p < 0.001 versus all groups, ^### p < 0.001 versus E2 or E3 at 12 months; E4 at 3 months, ^# p < 0.01 versus E3 18 months, ANOVA, Tukey–Kramer post test, ***p < 0.001, t test. B , ^& p < 0.001 versus all groups except E4 at 12 months, ^# p < 0.01 versus E4 at 3 months and E3 at 12 months, ANOVA, Tukey–Kramer post test, ***p < 0.001 t test. C , ^& p < 0.01 versus all other groups expect E3 at 18 months; ^# p < 0.01 versus all other groups except E4 at 18 months; ∧p < 0.01 versus E2 at 3 and 12 months, ANOVA, Tukey–Kramer post test, **p < 0.01, ***p < 0.001, t test. D , ^& p < 0.001 versus all other groups, ANOVA, Tukey–Kramer post test, ***p < 0.001, **p < 0.05 t test.