Abstract
Estrogens play a physiologically important role in the brain, but controversies exist regarding the association between Alzheimer's disease (AD) and estrogens. Estrogen-related factors were comprehensively examined in frontal lobe tissues from autopsied AD patients, and compared with controls. Concentrations of estrogens, expression of estrogen receptors (ERs), and estrogen-metabolizing enzymes (EMEs) which are important for determining the peripheral estrogen concentrations, were examined using liquid chromatography tandem mass spectrometry, immunohistochemistry, and quantitative real-time PCR, respectively. Body mass index (BMI), known to correlate with the serum estrogen concentrations, was also taken into consideration. There were no significant differences in estrogen concentrations or each EME level between the two groups in both the cortex and white matter, whereas glial nuclear ER-β expression was significantly lower in white matter from the AD group than the control group (Allred score, 3.2 ± 0.3 and 6.5 ± 0.3, respectively. P < 0.0001). Estrogen concentrations were found to closely correlate with BMI, particularly in controls. ER-β loss in the white matter from the AD group suggests the necessity of studying the effects of estrogens on glias as well as neurons in the etiology of AD. The correlation between BMI and estrogen concentrations in the frontal lobe suggests the importance of non-brain sources of estrogens.