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-ß (Aß) is central
to the pathology of AD. We investigated the effect of low doses
of conjugated estrogen (Premarin) in an animal model of Aß-induced
vascular disruption and inflammatory reaction. Estrogen prevented
vascular deposition of Aß, 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 Aß-induced vascular
dysfunction may contribute to the therapeutic efficacy of estrogen
in AD and coronary vascular disease.
