# INVESTIGATING THE EFFECTS OF MENOPAUSE-INDUCED EPIGENETIC MECHANISMS IN THE BRAIN

> **NIH NIH F31** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2023 · $47,455

## Abstract

ABSTRACT
More than 100 million people worldwide are estimated to be living with dementia in 2050. Age and sex are the
two most important factors determining Alzheimer’s disease (AD) incidence, with women’s lifetime risk double
that of men. As women live longer, the total number of women with AD substantially outnumbers men, making
the discovery of the molecular links between sex, age, and AD of the greatest significance. One hypothesis for
the higher prevalence of AD in women lies in the drastic changes in sex hormones women experience as they
traverse menopause, resulting in a depletion of estrogen and progesterone and metabolic changes. Altered
metabolism and increased deposition of Amyloid-β begins in peri-menopause and is accompanied by epigenetic
modifications, including histone acetylation, which impact on many critical pathways including mitochondrial
function. Women also have lower mitochondrial function in brain tissue than males, while new data from our lab
demonstrates that sexual dimorphism is observed in cognition and glucose metabolism in an aged AD mouse
model. Several reports have made epigenetic modification of histone proteins by histone acetyl transferases
(HATs) and histone deacetylases (HDACs) attractive drug targets in AD research. Our lab has shown that HDAC
inhibition improves memory in murine models of AD, simultaneously normalizing AD-pathology related molecular
changes (e.g. Aβ). To study the sequence of events I propose to utilize a murine model of AD and controlled
onset menopause to study epigenetic modifications, metabolism and AD-associated molecular changes that
occur during the onset and established ovarian failure. I hypothesize that both histone and non-histone acetyl-
group modifications occur during menopause resulting in metabolic dysfunction and acceleration of AD
pathology. I will identify acetylation and metabolic changes occurring during peri- and post-menopause-like
states in a murine model. These studies will aid in our understanding of the relationship between female sex and
AD with the long-term goal to help develop more personalized and/or sex-specific treatments by developing
evidence that there is a need for future drug trials to stratify AD patients based on sex.

## Key facts

- **NIH application ID:** 10728343
- **Project number:** 5F31AG076319-02
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Jessica Lee Dennison
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $47,455
- **Award type:** 5
- **Project period:** 2022-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10728343

## Citation

> US National Institutes of Health, RePORTER application 10728343, INVESTIGATING THE EFFECTS OF MENOPAUSE-INDUCED EPIGENETIC MECHANISMS IN THE BRAIN (5F31AG076319-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10728343. Licensed CC0.

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