APOE and Alzheimer disease: In this regard ApoE4 is considered detrimental, resulting in impaired copper export and elevated copper accumulation in astrocytes and neurons in vitro. This has been suggested to promote copper deficiency in AD, as astrocyte ApoE4-mediated copper retention could contribute to reduced neuronal copper availability since astrocytes are key to regulating brain copper levels (Scheiber and Dringen, 2013; Blades et al., 2024).