Vascular actions of estrogen and Alzheimer's disease.
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-beta (A beta) is central to the pathology of AD. We investigated the effect of low doses of conjugated estrogen (Premarin) in an animal model of A beta-induced vascular disruption and inflammatory reaction. Estrogen prevented vascular deposition of A beta, 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 A beta-induced vascular dysfunction may contribute to the therapeutic efficacy of estrogen in AD and coronary vascular disease.
Thomas
T
T
Woodlands Medical and Research Center, Oldsmar, Florida 34677, USA. tthomas1@tampabay.rr.com
Rhodin
J
J
D000544:Alzheimer Disease / Q000517:prevention & control; D016229:Amyloid beta-Peptides / Q000097:blood / Q000633:toxicity*; D000818:Animals; D001160:Arterioles / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000097:blood / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D013152:Splanchnic Circulation / Q000187:drug effects* / Q000502:physiology
D016229:Amyloid beta-Peptides; D004966:Estrogens, Conjugated (USP); D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40)