Estrogen regulates metabolism of Alzheimer amyloid beta precursor protein.

We have investigated the possible effect of estrogen on the metabolism of the Alzheimer amyloid precursor protein (APP). Using a cell line that contains high levels of estrogen receptors, we have found that treatment with physiological concentrations of 17 beta-estradiol is associated with accumulation in the conditioned medium of an amino-terminal cleavage product of APP (soluble APP or protease nexin-2), indicative of non-amyloidogenic processing. There were no obvious changes in the levels of intracellular immature or mature APP holoproteins, suggesting that estrogen may increase the secretory metabolism of APP.