# Inflammaging and ADRD: Investigating the Role of Complement and Alcohol.

> **NIH NIH R00** · UNIVERSITY OF COLORADO DENVER · 2020 · $245,748

## Abstract

PROJECT SUMMARY/ABSTRACT:
Alzheimer's' disease (AD) affects more than 5 million people in the United states and is a significant contributor
to dementia worldwide and to date, there is no cure. Because alcohol abuse is strongly associated with AD and
AD-related dementias (ADRD), we aim to expand the funded research award (R00AA025386) to understand if
alcohol-related liver disease is a contributing factor to neuroinflammation, neurodegeneration and cognition
impairment, thus contributing to early-onset AD progression. Moreover, as older individuals are more sensitive
to the detrimental effects of alcohol, we will investigate the role of liver-derived complement activation as a
component of “inflammaging” and ADRD. Importantly, we will use novel methods to assess the metabolic
consequences of chronic inflammation in the liver and brain by measuring bioactive lipid mediators, known as
oxylipins. Because neuroinflammation is a fundamental process contributing to neurodegeneration, and
persistent activation of complement contributes to chronic inflammation, It is our working hypothesis that
liver-derived complement activation, occurring after ethanol exposure, can perpetuate chronic
inflammation and tissue injury in the brain, leading to impairments in cognition during early-onset
ADRD. Findings from this supplement will be the first to describe complement as a key communicatory factor
participating in liver-brain crosstalk in AD caused by alcohol exposure. We will also be able to directly
investigate if alcohol-related liver disease is a causative factor for AD development. Importantly, findings from
these studies may provide new therapeutic targets to prevent the onset and progression of AD and ADRD.
This proposal, with explicit goals to better understand the biology of AD and ADRD, capitalizes on my
previously funded research, my expertise in cytokine biology, lipid oxidation and mechanistic toxicology, and
the established core facilities present at the University of Colorado. The experiments we propose are therefore
well within the scope of NOT-AG-18-008.

## Key facts

- **NIH application ID:** 10128155
- **Project number:** 3R00AA025386-05S1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Rebecca LeAnne Smathers McCullough
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $245,748
- **Award type:** 3
- **Project period:** 2018-09-30 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10128155

## Citation

> US National Institutes of Health, RePORTER application 10128155, Inflammaging and ADRD: Investigating the Role of Complement and Alcohol. (3R00AA025386-05S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10128155. Licensed CC0.

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