Estrogen-Related Factors in the Frontal Lobe of Alzheimer’s Disease Patients and Importance of Body Mass Index

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.

Estrogens, Aging, and Working Memory

“…However, lower endogenous estradiol levels compared with age-matched controls have been reported in women with actual or incipient Alzheimer’s disease (e.g., [ 66 ]). It is unclear at the present time whether or not lower peripheral levels are reflected in the central CNS concentrations of women who have Alzheimer’s [ 67 ] or whether replacement estrogens taken in the early postmenopause may help to protect against the accrual or progression of AD pathology [ 68 •, 69 , 70 ] in at-risk women.…”

An investigation into the potential association between nutrition and Alzheimer’s disease

“…Estradiol has been shown to improve cognition by mediating synaptic plasticity and increasing dendritic spine density (37), while testosterone has been shown to improve cognition by stimulating microglial phagocytosis, inhibiting neuroinflammation, and reducing Aβ deposition (38). A recent study found a significantly positive association between estrogen level and BMI in AD patients (39). It is well known that BMI is positively correlated with serum estrogen levels in postmenopausal women because of the high abundance of aromatase in adipose tissue (40).…”

Carcinogenesis of Triple-Negative Breast Cancer and Sex Steroid Hormones

“…Physiologically, androgens and estrogens are present in the body, with various rates among organs or individuals. The serum estrogen/androgen ratio is highest in premenopausal women, but lowest in postmenopausal women whose serum estrogen concentration is much lower than in men [ 42 , 43 , 44 , 45 , 46 , 47 ]. Intra- or peri-tumoral estrogen production is important in ER- and/or PR-positive tumors; however, TNBC or ER- and PgR-negative tumors, where local estrogen production is less active, are directly affected by the serum hormonal status [ 42 , 43 ].…”