# Contribution of Endothelial Changes and Increased Cardiovascular Risk to Alzheimer's Disease Pathogenesis

> **NIH NIH R03** · OKLAHOMA MEDICAL RESEARCH FOUNDATION · 2022 · $174,800

## Abstract

ABSTRACT
According to recent estimates, close to 6 million Americans are living with Alzheimer’s disease (AD), leading to
an estimated health cost of $290 billion. With the aging of the population, these numbers are expected to
substantially increase over time. Although AD has traditionally been considered to be a disease affecting only
neurons, there is an increasing appreciation for a vascular component; patients with AD often display
cerebrovascular alterations, and classical risk factors for cardiovascular diseases such as hypertension, have
been independently associated with an increased risk for dementia and AD. Although the exact mechanisms
underlying these observations are not fully understood, both disorders have been shown to affect the vasculature
leading to alterations in cerebral blood flow and degradation of the blood-brain barrier (BBB).
The goal of the studies proposed in this application is to test the hypothesis that high blood pressure acts in a
synergistic manner with AD-related pathology to augment endothelial dysfunction and subsequent BBB
degradation. To test this, we will evaluate changes in endothelial cell (EC) gene expression programs using an
in vivo EC-specific translating ribosome affinity purification (TRAP) approach, and correlate these to alterations
in cerebral blood flow and BBB permeability during the onset and progression of AD-related amyloidogenesis
and hypertension, either as separate entities or combined. The results of these studies will lead to a better
understanding of the molecular mechanisms underlying the early pathologic changes in the cerebrovasculature.
In addition, these data may result in the identification of early (preclinical) targets for future studies to assess
their application as a potential (blood-based) biomarker or as a target for therapeutic interventions. Particularly
for AD, as there is currently no cure and treatment options are mostly focused on reducing or controlling
symptoms, being able to identify the disorder in the preclinical stage would enable an early intervention and thus
increase the probability of therapeutic success.

## Key facts

- **NIH application ID:** 10471427
- **Project number:** 5R03AG070541-03
- **Recipient organization:** OKLAHOMA MEDICAL RESEARCH FOUNDATION
- **Principal Investigator:** Audrey Cleuren
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $174,800
- **Award type:** 5
- **Project period:** 2021-09-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10471427

## Citation

> US National Institutes of Health, RePORTER application 10471427, Contribution of Endothelial Changes and Increased Cardiovascular Risk to Alzheimer's Disease Pathogenesis (5R03AG070541-03). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10471427. Licensed CC0.

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