# The Role of Adenosine Kinase in Mixed Diastolic Heart Failure and Alzheimer Disease

> **NIH NIH F31** · AUGUSTA UNIVERSITY · 2024 · $44,597

## Abstract

PROJECT SUMMARY
Alzheimer’s disease (AD) is a prevalent disease with little understanding into the underlying mechanisms
behind the development of the disease. Diastolic dysfunction has been shown to be an independent risk factor
for the development of cognitive impairment. Patients with both diastolic heart failure (dHF) and AD represent a
population where therapeutic options are highly needed, but which unfortunately have minimal therapeutic
options due to a poor understanding of both diseases. Vascular dysfunction has been implicated in dHF and
AD. Due to a chronic inflammatory state, vascular endothelial dysfunction can occur, driving dHF/AD
pathologies. But little is known regarding the vascular endothelial mechanisms that contribute to cognitive
impairment. Specifically, adenosine kinase (ADK) plays an important role in regulating blood flow under
hypoxic conditions largely via its receptors (A1R, A2A/A2BR, and A3R). Pathologically, increased ADK is
implicated in neurodegenerative diseases, but its role in the vascular contributions underlying dHF/AD
pathologies is unknown. Thus, I hypothesize that augmented ADK activity impairs, whereas ADK
inhibition restores, cerebral parenchymal arteriole vasodilator function, mitigating the dHF-induced
worsening of cognitive decline and AD-related pathological outcomes. The goal of this project is to
examine the role of adenosine kinase in vasodilator function in a mixed dHF and AD pathology and to further
elucidate the underlying mechanisms of endothelial ADK in vasoreactivity. I will study this through the following
two Specific Aims. Aim 1. Test the hypothesis that increases in cerebrovascular ADK activity impair vasodilator
function of parenchymal arterioles, worsening cognitive dysfunction in mixed dHF/AD pathologies. Aim 2. Test
the hypothesis and mechanisms by which cerebrovascular endothelium-selective deletion of ADK restores
vasodilator function of small parenchymal arterioles in mixed dHF/AD. Through these aims, I will be able to
better elucidate the underlying vascular contribution in mixed dHF and AD pathologies as well as
mechanistically probe for the role of ADK in microvascular dysfunction and eventual cognitive impairment.

## Key facts

- **NIH application ID:** 10884190
- **Project number:** 5F31NS132564-02
- **Recipient organization:** AUGUSTA UNIVERSITY
- **Principal Investigator:** Katie Anne Fopiano
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $44,597
- **Award type:** 5
- **Project period:** 2023-07-01 → 2025-05-09

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10884190

## Citation

> US National Institutes of Health, RePORTER application 10884190, The Role of Adenosine Kinase in Mixed Diastolic Heart Failure and Alzheimer Disease (5F31NS132564-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10884190. Licensed CC0.

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