Changes in estrogen receptor-α and -β in the infundibular nucleus of the human hypothalamus are related to the occurrence of Alzheimer's disease neuropathology

The expression of estrogen receptor (ER)α and -β in the infundibular nucleus of the hypothalamus was studied immunocytochemically in 28 control subjects and 14 patients with Alzheimer’s disease (AD). A shift was found from more nuclear staining of ERα in young female controls to more cytoplasmic staining in elderly female controls, whereas no such change was observed in elderly male controls. The shift of ERα from nucleus to cytoplasm in elderly female controls was accompanied by a relative absence of AD neuropathology, i.e. hyperphosphorylated tau stained by hyperphosphorylated tau protein (AT8). In contrast, male and female AD patients showed more nuclear ERα and a much stronger AD neuropathology. It is proposed that the shift of ERα from nucleus to the cytoplasm may reflect activation of neurons and that hyperactivity decreases the risk that neurons in the course of aging develop AD neuropathology. In contrast, the presence of nuclear ERα seems to predispose to reduced activity and increases the risk o...