Before iCOs were used, neurons developed from iPSCs isolated from patients with FAD and SAD were used to demonstrate high Aβ peptide accumulation, tau phosphorylation, and endosomal alterations, all of which are early characteristics of AD (Cataldo et al., 2000; Israel et al., 2012; Muratore et al., 2014). This evidence concerns the gene MAPT and Alzheimer disease.