# Ovarian Hormone Regulation of Central and Cerebrovascular Hemodynamics

> **NIH NIH F32** · UNIVERSITY OF COLORADO DENVER · 2022 · $55,339

## Abstract

PROJECT SUMMARY
Alzheimer's disease (AD) is a major cause of morbidity and mortality in older adults that disproportionately
affects women. There are no effective treatments for AD in part because sex-differences in the
pathophysiology of AD remain unclear. However, increasing evidence supports the early role of extracerebral
(e.g., central artery stiffness) and intracerebral (e.g., reductions in cerebral blood flow and endothelial function)
vascular and mitochondrial dysfunction in the development of AD neuropathology. Menopause is associated
with increased oxidative stress and accelerated vascular aging with the loss of estrogen suggesting that
women may have an increased vascular contribution to the development of AD. The overall goal of this
research project is to investigate the role of declines in estrogen on the vascular contribution to brain aging in
women, and the underlying mechanism related to increased mitochondrial oxidative stress. {In humans,} we
will use both cross-sectional and intervention study designs to isolate the effects of estrogen deficiency on
changes in extra- and intra-cerebral vascular function in women. Healthy, pre- and post-menopausal women
without cognitive impairment will undergo baseline vascular testing. Additionally, premenopausal will undergo
12-weeks of gonadal suppression to temporarily and reversibly suppress ovarian hormones to investigate the
early vascular changes associated with estrogen deficiency. {To isolate changes in mitochondrial and
cerebrovascular function with estrogen deficiency, cerebral arterioles will be obtained from female
ovariectomized rats treated with degarelix and randomized to receive estrogen or placebo add-back for 10-
weeks. Cerebral endothelium-dependent and protein markers of mitochondrial function will be measured in
isolated cerebral arterioles.} Results of the proposed study will provide mechanistic insight into sex-differences
in AD risk in women and may inform novel future therapeutic targets for preventing or slowing the onset of AD
in women.
The applicant, Dr. Lyndsey DuBose, received graduate training in the extracerebral vascular contributions to
cognitive aging in humans at the University of Iowa. Dr. DuBose and her mentoring team have developed a
training plan that builds on her previous experiences to develop new skills in women's vascular health. Dr.
DuBose's training objectives are to obtain: 1) didactic training in clinical trial design, bioimaging, advanced
biostatistics, and reproductive endocrinology; 2) experience in conducting mechanistically-driven human
clinical translational research; 3) {develop basic science skills for the first time including the measurement of
mitochondrial and vascular function in female rats}; 4) produce several first-authored publications and improve
her grant writing skills in pursuit of becoming an independent clinical researcher in women's cardiovascular
and cerebrovascular aging.

## Key facts

- **NIH application ID:** 10548812
- **Project number:** 5F32AG071273-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Lyndsey DuBose
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $55,339
- **Award type:** 5
- **Project period:** 2021-09-30 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10548812

## Citation

> US National Institutes of Health, RePORTER application 10548812, Ovarian Hormone Regulation of Central and Cerebrovascular Hemodynamics (5F32AG071273-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10548812. Licensed CC0.

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