ESR1 and Alzheimer disease: Noradrenergic neurons of the LC express estrogen receptors, implicating estrogen as a key modulator of noradrenergic signaling within the brain.32 Estrogen exerts opposite effects on tyrosine hydroxylase activity, the rate-limiting step in catecholamine synthesis, in the LC in male and female brains.32,33 In contrast, sex-dependent effects of estrogen on noradrenergic signaling is an interesting component of AD.