Lack of protective effect of estrogens on cerebral Aβ levels in intact female and male APP transgenic mice

In previous experiments, treatment with either 17 beta-estradiol or 17 alpha-estradiol decreased cerebral beta-amyloid peptide (A beta) levels in ovariectomized female APP(SWE) transgenic mice, a mouse model for Alzheimer disease-like pathology. However, no effect of ovariectomy itself on cerebral A beta levels was observed. In the current study, intact female and male APP(IND,SWE) tran genic mice were treated chronically with oral 17 beta-estradioi or 17 alpha-estradiol. These treatments did not reduce cerebral A beta levels or amyloid plaque counts vs. vehicle treated mice. In fact, 17 beta-estradiol treatment of the intact female mice led to a significant increase in cerebral A beta levels.