# Cerebrovascular Mitochondrial Function in Aging and Ischemic Injury

> **NIH NIH R00** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2023 · $247,502

## Abstract

PROJECT SUMMARY/ABSTRACT
This research proposal has been developed to equip the candidate, Dr. Daniel Tyrrell, with knowledge,
experience, and skills to successfully transition into an independent faculty position. The proposed research
will examine mechanisms of why older adults are at increased risk of vascular disease. Vascular pathology in
the brain is present in up to 80% of people with Alzheimer’s disease (AD) and vascular dementia is the second
leading dementia behind AD. Dr. Tyrrell will have guidance from his mentors, Dr. Daniel Goldstein and Dr.
Michael Wang, and assistance from members of the Michigan Alzheimer’s Disease Research Center along
with experts in diverse fields who will contribute to Dr. Tyrrell’s training. Dr. Tyrrell has discovered that cerebral
blood vessels in aged mice have evidence of mitochondrial dysfunction leading to increased STING-IL-6
inflammation and blood-brain barrier breakdown. The mechanisms of vascular contributions to cognitive
impairment and dementias (VCID) in aging remain unclear. Therefore, the objective of this study is to
determine how cerebrovascular mitochondrial dysfunction impacts cognitive function in aging. Hence,
Aim 1 will determine how age-related cerebrovascular mitophagy and mitochondrial dysfunction impacts the
blood-brain barrier and cognitive function during natural aging and in a model of vascular dementia induced by
cerebral hypoperfusion. Aim 2 will examine how cerebrovascular inflammation impacts the BBB and cognitive
function in a model of vascular dementia with aging. Dr. Tyrrell will employ novel mitophagy reporter mice and
mice with enhanced mitochondrial function in addition to using cell-type specific conditional knockout mouse
models and pharmacologic approaches. Dr. Tyrrell will acquire both technical and scientific neurobiology
expertise in order to study blood-brain barrier integrity and cognitive function in aging to distinguish himself
from his mentors and allow him to develop a cutting-edge independent career in examining VCID.

## Key facts

- **NIH application ID:** 10693320
- **Project number:** 5R00AG068309-04
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Daniel Tyrrell
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $247,502
- **Award type:** 5
- **Project period:** 2021-04-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10693320

## Citation

> US National Institutes of Health, RePORTER application 10693320, Cerebrovascular Mitochondrial Function in Aging and Ischemic Injury (5R00AG068309-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10693320. Licensed CC0.

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