# Mechanisms by which CD74 Contributes to Traumatic Brain Injury

> **NIH NIH R01** · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · 2020 · $375,030

## Abstract

Summary.
Over 5 million Americans suffer from Alzheimer’s disease (AD) and related dementias (ADRD).
AD is an irreversible, incurable brain disorder, is the sixth leading cause of death in the U.S., and
accounts for as much as 60 to 70% of all forms of dementia. While genetic mutations account for
a small proportion of AD and ADRDs, the most common risk factor for dementia is prior central
nervous system (CNS) injury. Notably, traumatic brain injury (TBI) can accelerate the onset of
AD/ADRD, and increases AD risk by 2.3 - 4.5-fold. Thus, TBI is a significant risk factor for the
development of AD and ADRDs, and there are currently no effective treatments for AD or ADRDs.
Identifying novel therapeutic mechanisms and targets, is a critical preclinical and clinical need.
The complex hallmark brain changes that occur in AD include the appearance of abnormal clumps
in the brain, known as amyloid plaques, and tangled bundles of fibers, called neurofibrillary or tau
tangles. Inflammation and neuroinflammation are thought to play a major role in plaques and
tangles, and in numerous other aspects of AD pathogenesis. Interestingly, TBI induces
inflammatory responses that have been shown to exacerbate: AD pathology, neuropathology and
neurobehavioral deficits. An immune response can be considered to be non-specific, or specific,
and both have been implicated in AD/ and ADRDs. We have found that targeting a protein called
CD74, a component of both the non-specific (aka innate immune system) and specific immune
response (aka adaptive immune system), is neuroprotective after a TBI, and prevents cognitive
decline after TBI.
We propose that inhibiting CD74 after TBI will impede the development of AD-related
inflammation, neuroinflammation, neuropathology and neurobehavioral deficits. This work is a
natural extension of our currently funded proposal, in that we are already manipulating CD74 to
determine mechanisms of post-traumatic inflammation, neuroinflammation and neurobehavioral
decline. Here, we incorporate 5XFAD mice, and AD-specific outcome measures to determine if
targeting CD74 after TBI prevents detrimental neurobehavioral, neuropathological, and
immune/neuroimmune outcomes in the context of AD. We have assembled a research team
dedicated to successful completion of these important experiments, and each member possesses
expertise that is uniquely suited to make the sum of the parts greater than the sum of the whole.

## Key facts

- **NIH application ID:** 10123752
- **Project number:** 3R01NS104282-03S1
- **Recipient organization:** TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
- **Principal Investigator:** M. Karen Newell Rogers
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $375,030
- **Award type:** 3
- **Project period:** 2019-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10123752

## Citation

> US National Institutes of Health, RePORTER application 10123752, Mechanisms by which CD74 Contributes to Traumatic Brain Injury (3R01NS104282-03S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10123752. Licensed CC0.

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