Alzheimer's disease and estrogen

The preventive effect of estrogen on Alzheimer's disease (AD) has become clear with epidemiological data. Therapeutic effects of estrogen have not yet been established. In this presentation, we report our new basic and clinical data. The estrogen receptor, (ER), and ERβ mRNA were investigated in rat brain. Estradiol-17β (E₂) treatment following OVX reduced the levels of ER mRNA in the hypothalamus. In the substantia innominata (SI), the number of choline acetyltransferase immunoreacive cells increased significantly in the estrogen treatment rat. The neurons in SI projecting to the forebrain cortex contained ER. Increasing amounts of intracellular calcium, peroxidation, and apoptosis with amyloid β were suppressed in neuronal cells from rat pheochromocytoma (PC12) cells with E₂. ER cDNA transfected PC 12 cells elaborated more neurite-like processes with E₂. In clinics, we are currently preparing vaginal progesterone tablets, which essentially may concentrate in the endometrium to prevent endometrial cancer, with few general circulation of progesterone inviting less depression. The therapeutic effects of cyclic estrogen, such as its preventive effect, are suggested in these studies, at least on mild AD.