Estrogen and raloxifene activities on amyloid-beta-induced inflammatory reaction

The prevalence of Alzheimer's disease (AD) in women is double that of men. Several studies indicate that use of estrogen after menopause by women may reduce the risk of developing AD. The risk of estrogen-dependent tumors associated with estrogen replacement therapy has prompted the use of alternatives, like the SERM raloxifene, which exert estrogen agonist effects on selected target tissues. Whether SERMS provide cognitive and cardiovascular benefits comparable to those of estrogens is an active area of investigation in women's health. A chronic inflammatory process is central to the pathology of Alzheimer's disease. Using an animal model we compared the anti-inflammatory activity of orally administered estrogens (2 mg/kg) and raloxifene (3 mg/kg) in ovariectomized rats. Morphological analysis of Abeta(1-40)-induced inflammatory reaction featured adhesion and transmigration of leukocytes across the vessel wall, endothelial disruption, and platelet activation. Estrogen showed remarkable anti-inflammatory action, whereas raloxifene had no significant beneficial effect. Inhibition of the inflammatory process may contribute to the reported efficacy of estrogen in the treatment of AD.