Figure 13.
Sortilin is a major APOE uptake pathway relevant for neuronal catabolism of Aβ. A, Expression of APP, LRP1, and SORLA in the primary neuronal cell cultures of the indicated Sort1 genotypes as determined by Western blotting. Detection of tubulin served as loading control. B, Levels of Aβ40 were determined by ELISA in primary neurons from Sort1+/+ and Sort1−/− newborn mice incubated with the indicated two concentrations of lipidated APOE4 complexed with Aβ40. The data are mean ± SEM (n = 6) expressed as percentage of the respective (Sort1+/+) control. Statistically significant differences between genotypes were determined by Bonferroni's post hoc test (total degrees of freedom = 21; F = 31.06) and are indicated (**p < 0.01, ***p < 0.001). C, D, Levels of sAPPα and sAPPβ (C) and Aβ40 and Aβ42 (D) were determined by ELISA in primary hippocampal neurons either wild-type (PDAPP+/−; Sort1+/+; open bars) or homozygous for the Sort1 null allele (PDAPP+/−; Sort1−/−; filled bars). No statistically significant differences were seen for any of the APP processing products comparing genotypes (n = 9–14).