# Role of estradiol and related hormones on inflammation, sleep, and risks for Alzheimer's disease

> **NIH NIH R01** · EMORY UNIVERSITY · 2022 · $712,375

## Abstract

Women are more likely than men to develop Alzheimer's disease (AD), and available research
suggests this is not only because they have a longer life expectancy than men. This increased
risk is likely due, in part, to fluctuating sex hormones across the lifespan. Sex hormones likely
have direct actions on AD brain biomarkers (Aβ and tau levels), as well as indirect actions via
inflammation, sleep disruptions, and reduced brain blood flow and volume, all of which are
independent risk factors for AD. African Americans –men and women– are also at increased
risk for AD vs. Caucasians. As such, mechanistic studies and interventions need to be
thoroughly examined and tested in both African American and Caucasian participants. The
purpose of the proposed project is to determine the relationship between brain and systemic sex
hormones on known AD biomarkers in individuals most at risk for AD. 150 middle age, African
American (n=75) and Caucasian (n=75) women will be enrolled in this observational, two year
study. The main objectives are to test whether brain and serum sex hormones (estradiol,
estrone, progesterone, testosterone) differentially influence AD risk factors (inflammation, sleep
and cerebral blood flow,), and if sex hormone levels moderate the relationship between these
risk factors and AD biomarkers (cognition, CSF, neuro-imaging). We will leverage existing NIH
funded, well characterized cohorts (n=291; followed by MPIs Wharton & Hu), including middle-
age women at high risk for AD (through family history or APOE e4 allele) who already have
baseline and longitudinal blood, CSF, and MRI analysis for at least 2 years. We will also test our
hypotheses in a unique cohort enriched for African Americans based on our extensive track
record in recruiting and analyzing aging and AD biomarkers in a diverse cohort. Participants will
complete 3 study visits annually. At each year, we will collect medical and medication history,
subjective sleep, cognitive testing and questionnaires (stress, sleep, exercise, nutrition)
Participants also undergo blood draw for sex hormone and inflammatory markers. At Baseline
and Year 2, participants will undergo the aforementioned protocol, AND take part in: lumbar
puncture for spinal fluid collection, neuroimaging and will take home a non-invasive monitor for
collection of objective sleep data to wear for 1 night. We have assembled a multidisciplinary
team with complementary expertise in sex hormones and aging, AD biomarkers, inflammation,
neuroimaging, sleep, and biostatistics. Data inform larger NIH funded studies and, to our
knowledge, provide the largest and most comprehensive, biomarker driven, characterization of
brain and sex hormone levels in a racially diverse sample of middle-age women.

## Key facts

- **NIH application ID:** 10458043
- **Project number:** 5R01AG066203-04
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** William Tzu-lung Hu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $712,375
- **Award type:** 5
- **Project period:** 2019-09-15 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10458043

## Citation

> US National Institutes of Health, RePORTER application 10458043, Role of estradiol and related hormones on inflammation, sleep, and risks for Alzheimer's disease (5R01AG066203-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10458043. Licensed CC0.

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