PPIA and Cognitive impairment: 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.