We found that the average levels of the BACE1 substrate APP in other subjects were reduced compared to levels in subject AD1. There was a minor reduction of APP in subject AD2 but AD3, AD4 and AD5-derived 3D neurons expressed significantly less APP. The levels of APP were decreased 30–40% in these subjects compared to AD1. With a reduction of substrate APP, the efficacy of BACE1 inhibitor in these neuronal lines was better than in AD1.
