Objective: One mechanism to support the potentially beneficial effects of estrogen in the brain for postmenopausal women potentially involves the hormone's ability to favorably alter the processing of amyloid-precursor protein (APP), believed to play an important role in the pathobiology of Alzheimer disease (AD). The authors evaluated the effects of estrogen administration on plasma concentration of one by-product of APP processing, Abeta40, for postmenopausal women with AD.
Methods: In a placebo-controlled, double blind, parallel-group design study, 20 women were randomized to receive either 0.10 mg/day of transdermal 17beta-estradiol or a placebo for 8 weeks and were retrospectively evaluated as to whether basal levels of Abeta40 were affected by pre-study use of hormone replacement therapy (HRT). Blood samples were collected and cognitive tests were administered at baseline; at Weeks 3, 5, and 8 during treatment; and again 8 weeks after treatment termination.
Results: For the group as a whole, plasma Abeta40 was not reliably reduced in response to short-term estradiol administration. For HRT-naïve subjects, baseline Abeta40 concentrations were higher than those of previous HRT users, and controlled estradiol administration significantly reduced plasma Abeta40 by the end of the 8-week treatment period.
Conclusions: These results provide preliminary clinical evidence to support an effect of estradiol on Abeta-processing for AD women who are HRT-naïve. This finding suggests that the hormone may serve as an Abeta-lowering agent for HRT-naïve AD women, which may, in turn, have ultimate ramifications for the progression of AD pathology.