Sortilin deficiency increases plaque burden in the brain. A, Levels of Aβ40 were determined by ELISA in extracts of hippocampus (Hip) and cortex (Ctx) of 5xFAD mice either wild-type (5xFAD; Sort1+/+) or homozygous for the Sort1 null allele (5xFAD; Sort1−/−) at 2 months of age (n = 5–6 per group). B, Thioflavin S staining of sagittal sections through the brain of three to four individual mice at 2 and 10 months of age. Deposition of plaques (arrowheads) in the subiculum is seen in 2-month-old 5xFAD mice lacking sortilin (5xFAD; Sort1−/−) but not in the age- and gender-matched controls (5xFAD; Sort1+/+). At 10 months of age, a massive plaque burden is seen in both genotypes. Scale bar, 150 μm. C, Quantification of plaque burden in individual mice of the indicated age and genotype based on thioflavin S staining as exemplified in B (n = 2–6 sections per animal). *p < 0.05.