In this study, we administered human recombinant ANXA1 (hrANXA1) to young 5xFAD mice, a widely accepted model of Alzheimer’s disease, resulting in the reversal of cerebrovascular disruption and the reduction in amyloid-β pathology and memory loss at an early stage of Alzheimer’s disease. Here, ANXA1 is linked to early-onset autosomal dominant Alzheimer disease.