# Enduring effects of high estrogen on Alzheimer's disease

> **NIH NIH R03** · BAYLOR COLLEGE OF MEDICINE · 2021 · $320,000

## Abstract

ABSTRACT/SUMMARY
Women's obstetric history affects susceptibility to Alzheimer’s disease (AD). The number of pregnancies or the
number of children is positively correlated with the neuropathology of AD in several studies, while cumulative
estrogen exposure calculated from the number of menstrual cycles is associated with lower AD risk in another
study. The discrepancy may be due to differential estrogen levels, durations, and temporal patterns of exposure
in each setting. The protective effect of transient low-level estrogen during normal estrous cycles does not
necessarily mean that prolonged high-level estrogen exposure during pregnancy is beneficial. Few animal
studies have examined the effect of pregnancy-associated high-level estrogen exposure on late-life susceptibility
to AD. We intend to address this knowledge gap by determining how multiparity or high-level estrogen exposure
during the reproductive age affects late-life AD susceptibility in mice expressing amyloid precursor protein (APP)
with AD-causing mutations. We will also determine how multiparity during the reproductive age affects brain
gene expression in late-life using single-cell RNA-seq (scRNA-seq). Regarding the role of estrogen in AD risk,
most previous studies focused on the immediate effects of low estrogen in the context of estrogen hormone
replacement in the postmenopausal stage. In contrast, the enduring effects of high estrogen long after the
cessation of the exposure are unclear. Here, we examine the relationship between estrogen and AD from a novel
perspective of epigenomic memory, which may provide generalizable insight into how early- or mid-life
environmental factors modulate late-life AD risk.

## Key facts

- **NIH application ID:** 10110796
- **Project number:** 1R03AG070687-01
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Zheng Sun
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $320,000
- **Award type:** 1
- **Project period:** 2021-03-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10110796

## Citation

> US National Institutes of Health, RePORTER application 10110796, Enduring effects of high estrogen on Alzheimer's disease (1R03AG070687-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10110796. Licensed CC0.

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