# Inflammatory contributions of astrocytic RelA in comorbid VCID/AD

> **NIH NIH RF1** · UNIVERSITY OF KENTUCKY · 2020 · $2,006,540

## Abstract

PROJECT SUMMARY/ABSTRACT
Multiple lines of evidence in both humans and animal models suggest that neuroinflammation, mediated via
reactive gliosis, plays a critical role associated with the initiation and progression of vascular contributions to
cognitive impairment and dementia (VCID) and Alzheimer’s disease (AD), potentially suggesting convergent
pathophysiological mechanisms. In particular, several of these neuroinflammatory hallmarks in comorbid
VCID/AD animal models have been linked with the dysfunctional responses of reactive astrocytes. In the
healthy brain, it is well known that astrocytes play a critical role in maintaining a variety of homeostatic
mechanisms. However, as a response to injury or disease, astrocytes are able to rapidly respond, in a
generalized description referred as astrogliosis, with a variety of neuroinflammatory modalities, which recent
evidence suggests may cause dysfunctional responses of neurons. Contemporary work has demonstrated a
critical component to these dystrophic neuroinflammatory response of astrocytes is their utilization of canonical
NFkB (RelA) signaling pathway. However, relatively little is known regarding the role of RelA in astrocytes
exposed to the co-morbid degenerative milieu in VCID/AD, representing a critical knowledge gap for the field.
Our overarching hypothesis for this proposal is that astrocytic RelA represents a convergent
inflammatory mechanism driving dysfunctional sequelae in the comorbid VCID/AD milieu. This proposal
will examine three specific aims to determine how RelA utilization by astrocytes shapes both intrinsic and non-
cell autonomous dysfunctional responses to the comorbid VCID/AD degenerative environment:
 1. Determine the capacity of astrocytic-RelA in propagating inflammatory phenotypes of microglia and
 astrocytes in comorbid VCID/AD.
 2. Determine the role of astrocytic-RelA in driving cerebrovascular dysfunction in comorbid VCID/AD.
 3. Determine if synaptic and cognitive dysfunction in VCID/AD is linked with RelA expression in astrocytes.

## Key facts

- **NIH application ID:** 10054775
- **Project number:** 1RF1NS118558-01
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Josh Morganti
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,006,540
- **Award type:** 1
- **Project period:** 2020-09-15 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10054775

## Citation

> US National Institutes of Health, RePORTER application 10054775, Inflammatory contributions of astrocytic RelA in comorbid VCID/AD (1RF1NS118558-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10054775. Licensed CC0.

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