Remarkably, a similar E2F4 upregulation may also be observed in the AD prefrontal cortex [10] and in human neurons derived from familial AD (FAD) patient-specific hiPSCs [18] as well as in cortical neurons from 5xFAD mice [25], another AD mouse model that expresses human APP and PS1 containing five pathological mutations [26]. Here, PSEN1 is linked to Alzheimer disease.