Interestingly, over-expression of PSEN1-WT failed to prevent NPCs of A15-iPSC-3 from premature neuronal differentiation (Supplementary Figure 3g, Figure 4i-4k). The percentage of MAP2+ neurons was significantly higher in both vector transfected A15-NPC-3 (control) and PSEN1-WT-infected A15-NPC-3 cells than that in vector transfected N-NPC-1 controls (Figure 4j and 4k). The finding that WT PSEN1 could not correct the phenotypes in AD-NPCs during neuronal differentiation argues for a dominant nature of mutated PSEN1 in AD-NPCs.
