Submission Type

Poster

Abstract

Alzheimer’s Disease (AD) disproportionately affects females, with estrogen loss after menopause contributing to cognitive decline and metabolic dysregulation. The APOE4 genotype is the strongest genetic risk factor for late-onset AD and may interact with hormone fluctuations to exacerbate neurodegeneration in females. I am starting a project to test the role of estrogen in AD-related behaviors using APOE4 knock-in mice, which carry the high-risk AD allele. This female-focused study uses a mouse model to explore ovarian hormones in the context of AD risk. To begin, I assessed baseline estrous cycles in thirteen 8-month-old female APOE4 knock-in mice using a vaginal lavage technique, which allows for monitoring hormone-congruent cycle stages. To test if we could shift cyclicity, the mice were then placed on a ketogenic diet (KD)—a high-fat, low-carbohydrate diet that shifts brain metabolism from glucose to ketones. After this period, I reassessed their estrous cycles. In addition to monitoring weight, I tested memory using a working memory maze. This project is also developing a more quantitative and less invasive hormone tracking method. Currently, we are comparing traditional vaginal cytology with a digital hormone monitoring system using INITO fertility test strips, which measure estrogen, luteinizing hormone (LH), and progesterone through urine-based testing. This foundational work informs future experiments using ethinyl estradiol (EE)—a synthetic estrogen found in many birth control pills—to investigate how hormone treatments interact with age and APOE4 genotype. Ultimately, this research supports female-specific approaches to understanding and preventing AD.

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Sponsored by Allison Bechard

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228 - Investigating Metabolic and Hormonal Modulation in Female APOE4 Mice: Insights for Sex-Specific Alzheimer’s Research

Alzheimer’s Disease (AD) disproportionately affects females, with estrogen loss after menopause contributing to cognitive decline and metabolic dysregulation. The APOE4 genotype is the strongest genetic risk factor for late-onset AD and may interact with hormone fluctuations to exacerbate neurodegeneration in females. I am starting a project to test the role of estrogen in AD-related behaviors using APOE4 knock-in mice, which carry the high-risk AD allele. This female-focused study uses a mouse model to explore ovarian hormones in the context of AD risk. To begin, I assessed baseline estrous cycles in thirteen 8-month-old female APOE4 knock-in mice using a vaginal lavage technique, which allows for monitoring hormone-congruent cycle stages. To test if we could shift cyclicity, the mice were then placed on a ketogenic diet (KD)—a high-fat, low-carbohydrate diet that shifts brain metabolism from glucose to ketones. After this period, I reassessed their estrous cycles. In addition to monitoring weight, I tested memory using a working memory maze. This project is also developing a more quantitative and less invasive hormone tracking method. Currently, we are comparing traditional vaginal cytology with a digital hormone monitoring system using INITO fertility test strips, which measure estrogen, luteinizing hormone (LH), and progesterone through urine-based testing. This foundational work informs future experiments using ethinyl estradiol (EE)—a synthetic estrogen found in many birth control pills—to investigate how hormone treatments interact with age and APOE4 genotype. Ultimately, this research supports female-specific approaches to understanding and preventing AD.

 

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