APP and Alzheimer disease: To expand upon these findings and develop alternative human RO models of AD to better approximate the range of EOFAD mutations, we used two patient-derived hiPSC lines, one line with an APP duplication that results in cells with three copies of the APP gene, and one line harboring the “London” mutation in the APP gene, and we combined them with a well-established protocol for the generation of ROs (Zhong et al., 2014).