A–F , Levels of apoE in plasma, CSF, and brain homogenates in PDAPP mice expressing human apoE at various ages. A , B , ApoE levels in plasma ( A ) and CSF ( B ) were significantly greater in PDAPP/TRE2 mice, whereas the levels of apoE were the lowest in PDAPP/TRE4 mice. C , D , Soluble levels of apoE in hippocampal ( C ) or cortical ( D ) homogenates were significantly greater in PDAPP/TRE2 mice at all ages examined, whereas the levels of soluble apoE were significantly lower in PDAPP/TRE4 mice. E , F , Insoluble levels of apoE measured in the hippocampus ( E ) were significantly lower in PDAPP/TRE4 mice at a young age. There was an age-dependent increase in insoluble apoE levels in hippocampus ( E ) and cortex ( F ) of PDAPP mice expressing one of the human apoE alleles. A , ***p < 0.001 versus all other groups ANOVA, Tukey–Kramer post test, *p < 0.05 t test. B , ***p < 0.001 versus all other groups ANOVA, Tukey–Kramer post test, **p < 0.01 t test. C , ^∧∧∧ p < 0.001 versus all other groups, ^### p < 0.001 versus all other groups except ^# p < 0.05 versus E4 at 3 months ANOVA, Tukey–Kramer post test, *p < 0.05, **p < 0.01, ***p < 0.001 t test. D , ^∧∧∧ p < 0.001 versus all other groups, ^### p < 0.001 versus all other groups except E4 at 3 months, ^& p < 0.001 versus all other groups except E2 and E3 at 3 months ANOVA, Tukey–Kramer post test, **p < 0.05, ***p < 0.001 t test. E , ^& p < 0.001 versus all other groups except E4 at 18 months ^∧ p < 0.05 versus E3 at 12 months, ^# p < 0.05 versus E4 at 18 months, ANOVA, Tukey–Kramer post test, *p < 0.05 t test. F , ^& p < 0.001 versus all other groups, ^# p < 0.05 versus al other groups, ANOVA, Tukey–Kramer post test.