Collectively, the novel findings in this study are the followings: (i) ANXA1 and FPR2 are reduced in the Aβ42‐treated bEnd.3 cells and the capillaries of 5XFAD mice, (ii) ANXA1 is decreased in the serum of patients with AD, (iii) Aβ42 induced RhoA activation resulting in the disruption of the BBB, (iv) ANXA1 rescues Aβ42‐induced BBB disruption through the inhibition of RhoA‐GTP, (v) pericyte also regulates BBB integrity by secretion of ANXA1 and inhibition of RhoA‐GTP. This evidence concerns the gene ANXA1 and Alzheimer disease.