Alzheimer's disease and estrogen

The preventive effect of estrogen on Alzheimer's disease (AD) has become cl ear with epidemiological data. Therapeutic effects of estrogen have not yet been established. In this presentation, we report our new basic and clinic al data. The estrogen receptor, (ER)alpha, and ERP mRNA were investigated i n rat brain. Estradiol-17 beta (E-2) treatment following OVX reduced the le vels of ER alpha mRNA in the hypothalamus. In the substantia innominata (SI ), the number of choline acetyltransferase immunoreactive cells increased s ignificantly in the estrogen treatment rat. The neurons in SI projecting to the forebrain cortex contained ER alpha. Increasing amounts of intracellul ar calcium, peroxidation, and apoptosis with amyloid beta were suppressed i n neuronal cells from rat pheochromocytoma (PC12) cells with E-2. ER alpha cDNA transfected PC 12 cells elaborated Inore neurite-like processes with E -2. In clinics, we are currently preparing vaginal progesterone tablets, wh ich essentially may concentrate in the endometrium to prevent endometrial c ancer, with few general circulation of progesterone inviting less depressio n. The therapeutic effects of cyclic estrogen, such as its preventive effec t, are suggested in these studies, at least on mild AD. (C) 2001 Elsevier S cience Ltd. All rights reserved.