Graduation Year
2023
Document Type
Master's Thesis
Degree
Master of Science
Program
Biological Science
Program Director
Meredith Protas, PhD
First Reader
Pankaj Kapahi, PhD
Second Reader
Parminder Singh, PhD
Abstract
Menopause is a critical stage of ovarian aging that affects multiple other tissues. The imbalance of the hypothalamic-pituitary-ovarian (HPO) axis during menopause results in increased follicle-stimulating hormone (FSH) levels and a higher risk of Alzheimer's disease. Hormone replacement therapy is currently the only available option for treating menopause-related disorders, but it is expensive, short-term, and has various side effects. However, recent research indicates that blocking FSH with antibodies may improve Alzheimer's disease-related pathology in male and female mice, suggesting a new therapeutic strategy for menopause-related disorders. Methylglyoxal (MGO) accumulation during menopause is a significant obstacle to identifying safe and effective pharmacological interventions to treat menopause-induced Alzheimer's disease pathology. We propose modulating glycation burden using Gly-low, an MGO-lowering cocktail, as a safe alternative treatment to mitigate menopause-induced cognitive decline in a mouse model of Alzheimer's disease. We have demonstrated that Gly-Low can reduce FSH levels and improve cognition in ovariectomized 3xTg-AD mice, suggesting that compounds that protect against advanced glycation end products (AGEs) have the potential to prevent negative health complications that arise after menopause.