# Project 3: Peripheral Immune Activation on the Road to Development of Alzheimer's Disease: Therapeutic Targets and Windows

> **NIH NIH P01** · UNIVERSITY OF ARIZONA · 2022 · $370,515

## Abstract

PROJECT SUMMARY – PROJECT 3
Each year ~1.5 million American women enter into the perimenopause, a neuroendocrine transition state unique
to the female. The mission of the Perimenopause in Brain Aging and Alzheimer’s disease (P3) 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). Herein, we focus on the neuro-immune system as a key driver of
chronological and endocrinological aging that occurs in the midlife female brain. 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. Project 3 contributes to achieving P3 goals by determining
peripheral immune signatures at each stage of midlife chronological and endocrinological aging, their
contribution to the development of an at-risk-for AD phenotype, and identifying therapeutic interventions for AD
in the context of autoimmune disease (AID). Observations suggest that augmented adaptive cellular immunity
contributes to neurodegenerative changes seen in AD, that these changes are exacerbated during the
perimenopausal transition. The overall hypothesis guiding Project 3 is that peripheral inflammation during mid-
life endocrinological changes contributes to the development of AD and neurodegeneration later in the life of
females. Aim characterizes peripheral immunophenotypes that emerge during the perimenopausal transition,
evaluates the link between autoimmune flares and menopause, and identifies existing therapies for autoimmune
disease that are effective at reducing the risk of developing AD. The goal of Aim 2 is to identify mechanisms by
which the genetic risk factors APOE4 and HLA-DRB1*1501 contribute to development of AD and AID
phenotypes during the perimenopausal transition. The objective of Aim 3 is to determine the contribution of
immune activation by B-cell antigen presentation to neurodegeneration using. This objective will be achieved by
evaluating immunophenotype and neurodegenerative changes resulting from immunization of mouse models
from Aim 2 with amyloid beta or myelin oligodendrocyte glycoprotein. Outcomes of these studies will advance
our fundamental understanding of the role of systemic inflammation during perimenopause in the prodromal
neurodegenerative changes of AD and identify therapeutic interventions to reduce risk of AD in women with
autoimmune disorders (AID) who are already at higher risk of developing cognitive dysfunction.
Research proposed herein addresses strategic goals of the National Institutes on Aging’s 2016: Aging Well in
the 21st Century: Strategic Directions for Research on Aging, specifically Goals A1, 2, 3, 7, 8 & 11 and Goals
D1, 2, & 4.

## Key facts

- **NIH application ID:** 10412244
- **Project number:** 5P01AG026572-17
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** KATHLEEN E. RODGERS
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $370,515
- **Award type:** 5
- **Project period:** 2006-08-15 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10412244

## Citation

> US National Institutes of Health, RePORTER application 10412244, Project 3: Peripheral Immune Activation on the Road to Development of Alzheimer's Disease: Therapeutic Targets and Windows (5P01AG026572-17). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10412244. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*