# Perimenopause in APOE4 Brain: Clinical Outcomes and Global Impact (Project 3)

> **NIH NIH P01** · UNIVERSITY OF ARIZONA · 2020 · $440,489

## Abstract

PROJECT SUMMARY/ABSTRACT
The mission of our Perimenopause in Brain Aging and Alzheimer’s Disease Program Project is
to discover biological transformations in brain that occur during the perimenopausal transition
that lead to endophenotypes predictive of risk for Alzheimer’s disease (AD). Our goals are to
identify the mechanisms by which these transformations occur and to translate these
discoveries into strategies to prevent conversion to an at-Alzheimer's-risk phenotype.
The mission for this competitive Supplement to P01AG026572 Perimenopause in Brain
Aging and Alzheimer's Disease is to investigate whether the perimenopause to menopause
transition, a neuroendocrine transition state specific to the female, drives progression of
Alzheimer’s disease (AD) endophenotype in women, thereby playing a determinant role in the
well-established increased prevalence of AD in women. As late-onset AD accounts for the
greatest incidence and prevalence of the disease, determining sex-specific molecular
mechanisms relevant to AD onset and progression has the potential for greatest impact.
Further, examination of early stage transitions of risk has the greatest potential for identification
of therapeutic targets to change the trajectory of the disease to prevent, delay and potentially
reverse course of developing AD.
To achieve this goal, we propose to perform longitudinal multi-modality brain imaging
examinations in a cohort of prospectively recruited cognitively normal women at risk for AD, who
will undergo Magnetic Resonance (MR) and Positron Emission Tomography (PET) scans
measuring volumetrics, structural connectivity, mitochondrial bioenergetics, glucose
metabolism, and fibrillary amyloid-beta deposition at baseline and 2 years later.
Our plan is to leverage our active P01AG026572 (PI R. Brinton; Site-PI L. Mosconi) to perform
longitudinal exams on the 78 female patients who are scheduled to complete baseline
evaluations as part of the grant.
Outcomes of our analyses will elucidate molecular mechanisms that emerge in midlife and that
increase risk of developing AD later in life. Collectively, these data will provide therapeutic
targets for sex-based precision medicine interventions during the prodromal phase of late-onset
AD, when the potential to reverse, prevent and delay AD progression is greatest.
Research proposed herein address goals of the National Alzheimer's Project Act (NAPA) to
prevent and effectively treat AD by 2025 and the NIA Alzheimer's Disease Research Summit
2015 key objectives of sex and metabolic determinants of AD.

## Key facts

- **NIH application ID:** 10000011
- **Project number:** 5P01AG026572-15
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** ROBERTA EILEEN BRINTON
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $440,489
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10000011

## Citation

> US National Institutes of Health, RePORTER application 10000011, Perimenopause in APOE4 Brain: Clinical Outcomes and Global Impact (Project 3) (5P01AG026572-15). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10000011. Licensed CC0.

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