# Hematopoietic stem cell dysfunction in traumatic brain injury and Alzheimer's disease

> **NIH NIH F31** · CASE WESTERN RESERVE UNIVERSITY · 2024 · $53,974

## Abstract

PROJECT SUMMARY/ABSTRACT
Traumatic brain injury (TBI) is the greatest environmental risk factor for Alzheimer’s disease (AD). Although both
neurological conditions share many of the same pathological hallmarks including neurodegeneration, the
underlying mechanisms that establish this relationship between TBI and AD are not well understood. Acute TBI
transitions into chronic TBI, which is characterized by progressive neurodegeneration. The pathophysiologic
events associated with the transition of acute TBI into a chronic neurodegenerative condition can last for months,
years, or even a lifetime and are also thought to be associated with the pathogenesis of AD after TBI.
Investigating the mechanistic link between acute TBI, chronic TBI, and AD is important as there are currently no
therapeutic strategies to protect patients.
My proposed interdisciplinary project aims to address this knowledge gap by assessing the interplay between
TBI, hematopoietic stem cell (HSC) dysfunction, chronic neurodegeneration, and AD. Specifically, I am testing
the novel hypothesis that acute TBI induces changes to HSCs that in turn play a role in impairing the immune
system and propagating chronic neurodegeneration after TBI, and that these TBI-induced alterations are related
to the increased risk of AD after TBI. HSCs generate the entire spectrum of blood and immune cells, and my
preliminary studies thus far indicate that TBI induces major changes to HSCs, including impaired HSC function,
disrupted blood cell counts, and elevated inflammatory markers.
This study employs a clinically relevant model of TBI, cytometric analyses, and immunohistochemical
approaches to generate a deeper understanding of hematopoietic dysfunction in TBI and AD and the implications
of this dysfunction on the immune system and chronic neurodegeneration. Furthermore, this proposal is tailored
for a physician-scientist in training as it investigates the underlying mechanisms by which acute TBI transitions
into a chronic neurodegenerative condition, with implications for novel therapeutic targets for reducing
neurodegeneration after TBI and protecting TBI patients from developing AD.

## Key facts

- **NIH application ID:** 10995373
- **Project number:** 1F31NS139434-01
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Sofia Corella
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $53,974
- **Award type:** 1
- **Project period:** 2024-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10995373

## Citation

> US National Institutes of Health, RePORTER application 10995373, Hematopoietic stem cell dysfunction in traumatic brain injury and Alzheimer's disease (1F31NS139434-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10995373. Licensed CC0.

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