To understand how SORL1 truncating variants may impact the onset and progression of AD, we generated cortical excitatory neurons from induced pluripotent stem cells (iPSCs) derived from an individual clinically diagnosed with AD and carrying a truncating SORL1 mutation at exon 20 (Figure 1A), who was also homozygous for the APOE4 allele, which independently increases the risk for AD by approximately 12-fold (Kim et al., 2009). The gene discussed is APOE; the disease is Alzheimer disease.