# CTBI:CBI Tauopathy in Mice and Human: Neurodegeneration after Repetitive Neurotrauma: Mechanisms and Biomarker Discovery

> **NIH VA I01** · VA BOSTON HEALTH CARE SYSTEM · 2020 · —

## Abstract

Blast exposure is the leading cause of traumatic brain injury among U.S. forces deployed to Afghanistan and
Iraq, yet alarmingly little is known about the pathological consequences of blast exposure because so few
human brains have been studied. Our studies of over 500 brains of contact sport athletes and military veterans
exposed to blast and concussive injury have shown that both blast and concussive impact injuries are
associated with microvascular dysfunction, neuroinflammation, astrocytosis, hyperphosphorylated tau (ptau)
deposition and the development of chronic traumatic encephalopathy (CTE), a posttraumatic
neurodegeneration. CTE is defined pathologically by the perivascular accumulation of hyperphosphorylated tau
(ptau) protein and results in progressive decline in cognitive, behavioral and mood function. There is a critical
need to comprehensively examine more veteran cases of blast injury in order to determine the precise
pathobiology underlying the late-effects of these injuries and to develop biomarkers to detect the specific, yet
evolving, molecular, cellular, and anatomical brain changes induced by blast exposure. Given that 300,000
military veterans have been exposed to blast, there is urgency to recruiting brain donation from these veterans
and analyzing the effects of blast on critical brain processes. Understanding the neuropathology of blast-
induced brain changes will identify ways to detect these alterations during life and to monitor the development
of posttraumatic neurodegeneration and CTE. In this application, we will use the largest neuropathologically
confirmed autopsy cohort of veterans exposed to blast and concussive injury, in conjunction with a robust
recruitment effort to dramatically increase the number of brain donors, to determine the relationship between
blast exposure and neuroinflammation, blood brain barrier leakage, astrocytic degeneration, loss of the
glymphatic clearance network and ptau pathology. We will use cutting edge neuropathological techniques
including quantitative immunohistochemistry, multiplex immunofluorescence, quantitative polymerase chain
reaction (qPCR) expression analysis, enzyme-linked immunosorbent assay’s (ELISA), in
situ hybridization (ISH) and gene expression assays in veterans with a history of blast injury, veterans and
contact sport athletes with a history of concussive impact injury and veteran controls to gain new insights into
the molecular mechanisms underlying blast-induced posttraumatic neurodegeneration and CTE. We will also
test whether APOEε4 and TMEM106b haplotype status modify these effects. This research will pave the way
towards identifying novel biomarkers for detection and targets for early therapeutic intervention in blast-induced
posttraumatic neurodegeneration and CTE. Understanding the fundamental pathophysiology underlying
microvasculopathy, inflammation, astrocytosis, aquaporin loss and accelerated ptau pathology after exposure
to blast and concussive impact...

## Key facts

- **NIH application ID:** 9782235
- **Project number:** 1I01BX004613-01
- **Recipient organization:** VA BOSTON HEALTH CARE SYSTEM
- **Principal Investigator:** Ann C. McKee
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2020-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9782235

## Citation

> US National Institutes of Health, RePORTER application 9782235, CTBI:CBI Tauopathy in Mice and Human: Neurodegeneration after Repetitive Neurotrauma: Mechanisms and Biomarker Discovery (1I01BX004613-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9782235. Licensed CC0.

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