Sortilin deficiency selectively increases Aβ levels in the murine brain. A, B, Levels of murine APP protein (A; mAPP) and App mRNA (B) are unchanged in extracts of sortilin-deficient (Sort1−/−) compared with control (Sort1+/+) mouse brains as shown by Western blotting and quantitative RT-PCR, respectively (n = 4 per genotype for B). C, D, Cortical levels of human APP protein (hAPP) are identical when comparing Sort1+/+ and Sort1−/− mice on the PDAPP background by Western blotting (C) and densitometric scanning of replicate blots (D; n = 3 per genotype). E, Levels of sAPPα, sAPPβ, and Aβ40 were determined by ELISA in brain extracts of PDAPP wild-type mice (PDAPP+/−; Sort1+/+; white bars) or mice homozygous for the Sort1 null allele (PDAPP+/−; Sort1−/−; black bars) (n = 3–7 per group). F, G, Aβ40 levels in hippocampus (Hip) and cortex (Ctx) of mice of the indicated genotypes at 5 months (F; n = 3–5 per group) and 9 months (G; n = 8–10 per group) of age. Values are mean ± SEM.