In support of this approach, hCOs with APP and PSEN1 mutations, hCOs generated from Down syndrome iPSCs, and hCOs carrying the Alzheimer disease (AD) APOE4 risk allele show AD hallmarks, including amyloid-beta accumulation and tau hyperphosphorylation (Raja et al., 2016; Gonzalez et al., 2018; Lee et al., 2016). This evidence concerns the gene PSEN1 and Alzheimer disease.