Toward this, we have comprehensively investigated AD-related pathogenic pathways using iPSC-derived 3-D cerebral organoids from sporadic AD patients with or without APOE4. cerebral organoids not only simulate intrinsic spatial patterning, but also display acquisition of cell identity in a timed manner that closely mimics the temporal patterning with sequential neuronal layer formation, accompanied with matured astrocytes21,22,33. Here, APOE is linked to Alzheimer disease.