The novel estrogen receptor beta agonist EGX358 and genotype influence memory, vasomotor, and anxiety outcomes in an Alzheimer's mouse model.

Introduction: Alzheimer's disease (AD) prevalence and severity are associated with increased age, female sex, and apolipoprotein E4 (APOE4) genotype. Although estrogen therapy (ET) effectively reduces symptoms of menopause including hot flashes and anxiety, and can reduce dementia risk, it is associated with increased risks of breast and uterine cancer due to estrogen receptor alpha (ERα)-mediated increases in cancer cell proliferation. Because ERβ activation reduces this cell proliferation, selective targeting of ERβ may provide a safer method of improving memory and reducing hot flashes in menopausal women, including those with AD.

Estradiol improves behavior in FAD transgenic mice that express but not after ovariectomy.

Increasing evidence suggests that female individuals have a higher Alzheimer's disease (AD) risk associated with post-menopausal loss of circulating estradiol (E). However, clinical data are conflicting on whether E lowers AD risk. One potential contributing factor is .

APOE2 Heterozygosity Reduces Hippocampal Soluble Amyloid-β42 Levels in Non-Hyperlipidemic Mice.

APOE2 lowers Alzheimer's disease (AD) risk; unfortunately, the mechanism remains poorly understood and the use of mice models is problematic as APOE2 homozygosity is associated with hyperlipidemia. In this study, we developed mice that are heterozygous for APOE2 and APOE3 or APOE4 and overexpress amyloid-β peptide (Aβ) (EFAD) to evaluate the effect of APOE2 dosage on Aβ pathology. We found that heterozygous mice do not exhibit hyperlipidemia.

A novel apoE-mimetic increases brain apoE levels, reduces Aβ pathology and improves memory when treated before onset of pathology in male mice that express APOE3.

Background: Alzheimer's disease (AD) is characterized by cognitive dysfunction and amyloid plaques composed of the amyloid-beta peptide (Aβ). APOE is the greatest genetic risk for AD with APOE4 increasing risk up to ~ 15-fold compared to APOE3. Evidence suggests that levels and lipidation of the apoE protein could regulate AD progression.

genotype and sex modulate Alzheimer's disease pathology in aged EFAD transgenic mice.

Increasing evidence supports that age, and sex interact to modulate Alzheimer's disease (AD) risk, however the underlying pathways are unclear. One way that AD risk factors may modulate cognition is by impacting amyloid beta (Aβ) accumulation as plaques, and/or neuroinflammation Therefore, the goal of the present study was to evaluate the extent to which age, and sex modulate Aβ pathology, neuroinflammation and behavior . To achieve this goal, we utilized the EFAD mice, which express human or and have five familial AD mutations (FAD) that result in Aβ42 overproduction.