Utilizing the murine brain endothelial cell line (bEnd.3) and the 5XFAD transgenic AD mouse model, we have shown that Aβ42‐induced BBB disruption is mediated by the RhoA‐ROCK signaling pathway and showed that ANXA1 can alleviate the BBB breakdown through inhibition of the RhoA‐ROCK signaling pathway. Here, RHOA is linked to Alzheimer disease.