Vascular Actions of Estrogen and Alzheimer's Disease

A bstract : Women are two to three times more likely to develop late‐onset Alzheimer's disease (AD) than age‐matched men. A large number of observational reports and a few randomized clinical trials have indicated that estrogen replacement therapy (ERT) may retard the development and severity of dementia in postmenopausal women. A chronic inflammatory reaction mediated by abnormal deposition of proteins such as amyloid‐β (Aβ) is central to the pathology of AD. We investigated the effect of low doses of conjugated estrogen (Premarin) in an animal model of Aβ‐induced vascular disruption and inflammatory reaction. Estrogen prevented vascular deposition of Aβ, endothelial and vessel wall disruption with plasma leakage, platelet and mast cell activation, and characteristic features of an inflammatory reaction: adhesion and transmigration of leukocytes. The beneficial effect was lost when estrogen treatment was discontinued. This novel protective effect of estrogen against Aβ‐induced vascular dysfunction may contribute to the therapeutic efficacy of estrogen in AD and coronary vascular disease.