A crucial role of APOE4 in AD pathogenesis is highlighted by Zhao and colleagues; the authors obtained cerebral organoids from both cognitively unimpaired and impaired individuals carrying the APOE ε3/ε3 or ε4/ε4 genotype, demonstrating that APOE ε4/ε4 worsens tau pathology in both organoids from AD patients and healthy individuals, but larger amounts of ab and phospho-tau are found in AD patients. Here, APOE is linked to Alzheimer disease.