Fig. 4.

Sortilin deficiency decreases FABP7 levels in brains of apoE3 but not apoE4 mice. (A,B) Western blot analysis of FABP5 and FABP7 levels in brain cortices of apoE3 (A) and apoE4 (B) targeted replacement mice, either wild-type (WT) or homozygous for the Sort1 null allele (KO) (at 3 months of age). Na/K ATPase and GAPDH served as loading controls for detection of FABP5 and FABP7, respectively. Detection of sortilin served as genotype control. (C) Quantitative analysis of FABP7 levels in brain cortices of apoE3- and apoE4-expressing mice of the indicated Sort1 genotype using densitometric scanning of replicate western blots. Values are mean±s.e.m. given as percentage of the respective WT control (set to 100%); n=16 for E3/WT, n=18 for E3/KO, n=12 for E4 groups. **P<0.01 between genotypes (unpaired, two-tailed Student t-test). (D) Levels of Fabp7 transcripts in brain extracts (cortex and hippocampus) of apoE3- and apoE4-expressing mice of the indicated Sort1 genotypes as determined by quantitative RT-PCR. Values are given as mean±s.e.m. (n=5 for E3 groups, n=6 for E4/ WT, n=8 for E4/KO). No statistically significant differences in transcript levels were observed using unpaired, two-tailed Student's t-test. (E,F) Western blot analysis of FABP5 and FABP7 levels in prefrontal cortex specimens of AD patients homozygous for APOEε3 or APOEε4 (pathological characteristics given in Table S2). A representative western blot is shown in E. Detection of GAPDH served as loading control. F shows the result of densitometric scanning of replicate blots. Values are mean±s.e.m. given as percentage of APOEε3/3 genotype (mean value set to 100%); n=12–34 individuals per group. *P<0.05 (Welch's t-test).