In the dysfunctional NVU, astrocytic apolipoprotein E4 (APOE4), interacting with pericytic low-density lipoprotein receptor-related protein 1, through cyclophilin A (CypA) signaling, increases MMP-9 transduction and thrombin/PAR-1 signaling.25The BBB breakdown was more severe in carriers of APOE4, an identified genetic risk factor for AD with cognitive impairment, independently of AD biomarkers, both Aβ and tau. The gene discussed is APOE; the disease is Cognitive impairment.