Estrogen receptors alpha and beta in choroid plexus epithelial cells in Alzheimer's disease

Estrogen replacement therapy (ERT) may reduce the risks of Alzheimer's disease (AD). One of the potential actions of estrogen is through its effect on beta-amyloid elimination into the cerebrospinal fluid (CSF) compartment from the brain parenchyma. CSF secretion is controlled largely by the choroid plexus (CP) epithelial cells. In this study, we evaluated the status of estrogen receptor (ER) alpha and beta subtypes in CP epithelial cells. Tissue from 49 AD and 12 non-AD patients were studied using immunohistochemistry with anti-ER antibodies. ER alpha and ER beta were present in CP epithelial cells in both cytosolic and nuclear compartments. Male and female AD patients had lower ER alpha and beta densities in CP compared to non-AD patients. We further stratified the female AD patients into four groups according to their hormonal status. Among the female AD patients, those without hysterectomy and with ERT had the highest ER alpha density. In contrast, those with hysterectomy and without ERT had the lowest ER alpha density. The effects of hysterectomy and ERT were additive. For ER beta, ERT but not the status of hysterectomy was associated with higher receptor density. The lower ER density in CP epithelial cells of AD patients supports a potential role of estrogen in the regulation of CSF secretion of beta-amyloid protein, which may affect the accumulation of beta-amyloid in the brain parenchyma. Among AD patients, the association of ER alpha density with status of hysterectomy and ERT supports estrogen effects through receptor-mediated mechanisms.