Figure 4

AD-E3/E4 BFCNs have elevated Aβ42/Aβ40 ratios and altered responses to γ-secretase inhibitors. Medium conditioned by 300,000 neurons for 72 hours was assayed simultaneously for soluble Aβ40 and Aβ42 by sandwich ELISA. Levels of Aβ secretion were normalized to cellular protein. (A) Aβ42 levels were significantly elevated in familial AD line AG07872 and ApoE3/E4 lines AG04402 and AG11414 compared to the average of controls (n = 4, mean ± SEM, one-way ANOVA, p < 0.0001, F(5,36) = 24.16; Bonferroni multiple comparisons, **p < 0.01, ****p < 0.0001). (B) The ratios of secreted Aβ42 to Aβ40 were compared to the average of controls (n = 4, mean ± SEM, one-way ANOVA, p < 0.0001, F(5,36) = 34.70; Bonferroni multiple comparisons, ****p < 0.0001). (C, D) Quantification of Aβ40 secretion in response to different dosages of γ-secretase inhibitor compound E (C) or DAPT (D) treatment. (n = 3, mean ± SEM, Student’s t-test, *p < 0.5, ***p < 0.001), n indicates number of replicative experiments from the same line.