Emerging evidence suggests that APOE ɛ4 directly impairs the BBB: astrocyte-secreted ApoE4 induces the degeneration of brain capillary pericytes that maintain BBB integrity (Bell et al., 2012), and individuals carrying APOE ɛ4 are closely linked to the onset and progression of AD pathogenesis, independent of pathological Alzheimer’s biomarkers (Montagne et al., 2020; Uchida et al., 2022a). Here, APOE is linked to Alzheimer disease.