(A, B) Levels of murine (m) APP protein (A) 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 (h) APP protein are identical 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 soluble (s) APPα, sAPPβ, and Aβ40 were determined by ELISA in brain extracts of PDAPP mice wild-type (PDAPP+/−, Sort1+/+; white bars) or 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 of age (G; n=8–10 per group). Values are mean ± SEM.