# Neuronal exosomes to identify biomarkers and pathology of deployment-related TBI

> **NIH VA I01** · VA SAN DIEGO HEALTHCARE SYSTEM · 2021 · —

## Abstract

Traumatic brain injury (TBI) is a signature injury of OIF/OEF Veterans. More than 360,000 armed service
members sustained TBI during combat and training from 2000 to 2016. There is currently no diagnostic
biological marker for TBI nor can current diagnostic tools identify individuals at greatest risk for chronic
neurological and subsequent functional impairments after TBI. Neuronally-derived exosomes (NDEs)
obtained from peripheral blood may be a powerful tool to develop accessible CNS-based biomarkers
associated with neuronal dysfunction, particularly in relation to long-term brain injury and
neurodegeneration. Our recently published work demonstrates that neuropathological proteins (e.g
betaamyloid, Aß, and tau) within NDEs can predict conversion from mild cognitive impairment to
Alzheimer's Disease (AD) while plasma levels do not. Studies of NDEs are now being tested as companion
biomarkers in AD clinical trials to help reduce screen fail rates and increased enrollment. We have recently
found that cytoskeletal and synaptic proteins are also abnormal in deployment-related TBI patients >3 mo
after TBI. Specifically, both Aß and neurogranin are altered in plasma NDEs from participants who
experienced a deployment-related TBI. Taken together, our data support the hypothesis that plasma NDEs
may be a powerful tool to identify accessible and CNS-specific protein biomarkers for TBI. NDEs are also
enriched for short length “micro” RNA (miRNA) cargo. Each miRNA can regulate protein expression from
hundreds of target messenger RNAs, providing an efficient mechanism to exert genome-wide regulation
and simultaneously affect several cellular pathways. miRNAs confer tissue specificity and have recently
emerged as potential biomarkers and therapeutic targets for neurodegeneration. Hence, identification of
CNS-specific miRNAs associated with NDEs may provide a window to the pathogenic processes in chronic
TBI for future intervention. We hypothesize that proteins related to neurodegeneration within NDEs,
such as Aß, as well as miRNAs associated with NDEs have the potential to be biomarkers of TBI and
associated symptoms. To test this hypothesis we will leverage our prospective longitudinal study of
combat deployment effects in >1200 Marines, of which 176 experienced mild/moderate deployment-related
TBI. This study collected physical and mental health, neurocognitive performance and blood samples 1 mo
before and 4-6 mo after a combat deployment to Afghanistan. We will use 150 TBI samples with 150
samples of matched controls with no TBI history to complete 2 aims. Aim 1 will examine utility of
cytoskeletal and neuronal proteins in NDEs to identify TBI in addition to persistence of post-concussive
symptoms and cognitive decline. Candidate neurodegenerative proteins include tau, Aß, neurogranin,
neurofilament light chain and calpain-cleaved αII-spectrin N-terminal fragment. Studies will also leverage
these prospective samples to examine if change in NDE proteins f...

## Key facts

- **NIH application ID:** 10046280
- **Project number:** 5I01BX004312-03
- **Recipient organization:** VA SAN DIEGO HEALTHCARE SYSTEM
- **Principal Investigator:** Victoria B Risbrough
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-10-01 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10046280

## Citation

> US National Institutes of Health, RePORTER application 10046280, Neuronal exosomes to identify biomarkers and pathology of deployment-related TBI (5I01BX004312-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10046280. Licensed CC0.

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