ApoE protein, which exists in several isoforms, plays a crucial role in lipid metabolism, Aβ deposition, and OS.ApoE4 has the lower antioxidant capacity compared to ApoE2 and ApoE3, due to its reduced ability to bind and neutralize lipid peroxidation products such as HNE → presence of the ApoE4 allele is associated with increased OS.ApoE4 is a significant genetic risk factor for AD.Mitochondrial dysfunction, which is influenced by genetic factors → increased ROS production.Reduced activity of SIRT3 → increased ROS production → neurodegeneration [67,68,69,70]. The gene discussed is APOE; the disease is Alzheimer disease.