# Microanalytical Peptide-Peptidase Profiling of the Brain Renin-Angiotensin System in a Genetically Diverse Alzheimer's Disease Mouse Model

> **NIH NIH R21** · UNIV OF MARYLAND, COLLEGE PARK · 2024 · $443,365

## Abstract

Summary/Abstract
High blood pressure is considered a risk factor for dementia and Alzheimer's disease (AD)
progression. The renin-angiotensin system (RAS) is a hormonal and neuropeptide system that
regulates blood pressure and is implicated in cardiovascular-neurodegenerative diseases, and
as a potential target for dementia and AD treatment. While the function of the circulatory RAS in
diseases such as hypertension is well-known, its role in the brain particularly in brain areas
affected by dementia and AD remains unclear. Using a genetically diverse humanized AD
mouse model and new-generation ultrahigh-sensitivity mass spectrometry, this proposal will
focus on elucidating the role of the brain RAS and hypertension risk in AD. We will focus our
efforts across three objectives: (1) Measure the profiles of brain angiotensin peptides and
peptidases in genetically diverse AD-BXD mice and the impact of susceptibility and resilience to
late-onset Alzheimer's disease (LOAD); (2) Determine the effects of hypertension on the
angiotensin peptide–peptidase profiles in the early-onset (6 mo.) susceptible strains; (3) Utilize
bioinformatic tools for multivariate-statistical data analysis to uncover connections between the
angiotensin peptide-peptidase system of the brain and the intricate interplay among cognitive,
cardiovascular, behavioral, sex-dependent, and neuropathological factors, and whether these
relationships contribute to the susceptibility and progression of dementia and the risk of
developing AD. These investigations hold the potential to unveil new biological mechanisms that
contribute to dementia and AD risk and provide the opportunity for identifying new therapeutic
directions that could potentially prevent or slow down the progression of dementia and AD.

## Key facts

- **NIH application ID:** 10870915
- **Project number:** 1R21AG086859-01
- **Recipient organization:** UNIV OF MARYLAND, COLLEGE PARK
- **Principal Investigator:** Paul J Marvar
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $443,365
- **Award type:** 1
- **Project period:** 2024-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10870915

## Citation

> US National Institutes of Health, RePORTER application 10870915, Microanalytical Peptide-Peptidase Profiling of the Brain Renin-Angiotensin System in a Genetically Diverse Alzheimer's Disease Mouse Model (1R21AG086859-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10870915. Licensed CC0.

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