of PSEN1-A246E in N-iPSC-1 drastically reduced percentage of BrdU+ proliferative cells, while no alteration was found in PSEN1-WT transduced cells (Figure 4e and 4f). In addition, introduction of PSEN1-A246E into N-iPSC-1 increased the percentage of TUNEL+ apoptotic cells during differentiation (Figure 4g and 4h). Therefore, the introduction of mutated PSEN1 into N-iPSCs produced similar early neural dysfunctions as seen in AD-iPSCs during neuronal differentiation. However, over-expression of PSEN1-A246E in N-iPSC-1 cells did not affect the maintenance of N-NPCs, as evidenced by normal survival, proliferation and expression of NPC markers in NPCs derived from the PSEN1-A246E-transfected N-iPSC-1 cells (Supplementary Figure 3b-3f).
