# Chronic effects of blast injury: analyses of Alzheimer related pathology

> **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2020 · —

## Abstract

DESCRIPTION (provided by applicant):    
Blast-induced traumatic brain injury (blast TBI) is considered the signature injury of current military conflicts. Veterans exposed to blast TBI suffer concussions and neurological deficits, and are at increased risk for developing chronic neurological disorders including chronic traumatic encephalopathy and Alzheimer's disease (AD). Rehabilitation of blast-injured Veterans and prevention of chronic neuropathology is an area of medical research in need of intensive investigation because long-term effects of blast TBI are currently unknown and there are no treatments for improving long-term functional recovery after blast TBI. Our preliminary studies demonstrate that experimental blast TBI in mice impairs cognitive, vestibulomotor and sensory (visual) function, and these deficits are accompanied by changes in amyloid-¿ (A¿) and tau proteins which comprise the hallmark neuropathology of AD. We propose to use the transgenic APPswe,PSEN1dE9 mouse model, which recapitulates several aspects of age- and injury-induced A¿ pathology, to test the hypothesis that repetitive mild blast injury accelerates the onset and/or aggravates the onset and progression of A¿ accumulation and induces excessive tau phosphorylation (p-tau), exacerbating synaptic loss and functional impairment. These changes will be examined in relation to performance on spatial memory and vestibulomotor tasks during the chronic rehabilitation period after blast TBI. We also hypothesize that blast injury impairs retinal function, and propose to evaluate if such deficit could serve as an early diagnostic indicator of blast-induced damage to the brain. Additional biomarker analyses of diagnostic and potential prognostic values will include diffusion tensor imaging (DTI) and measurements of A¿ and p-tau concentration in cerebrospinal fluid (csf) and plasma. These studies will provide the framework for another major goal of this proposal, which is to test the therapeutic value of simvastatin, an FDA- approved drug currently in use for treatment of hypercholesterolemia and markedly effective in improving outcome in several models of brain injury. We will first characterize A¿ and p-tau pathology and functional (visual, vestibulomotor, cognitive) deficits during the chronic recovery phase (3, 6, 9, and 12 months) after single or repetitive mild (20 psi) grade blast exposure in the APPswe,PSEN1dE9 and C57Bl/6 wild type mice (Aim 1). The second major goal is to assess whether acute, transient (3 month) or continuous chronic (duration of survival period) daily simvastatin administration will prevent early onset of, and/or reduce, A¿ and p-tau pathology and improve functional recovery after blast injury in APPswe,PSEN1dE9 mice compared to C57Bl/6 wild type mice evaluated 3, 6, 9, and 12 months after injury (Aim 2). Thirdly, we will determine how chronic sequelae of blast injury, with or without simvastatin intervention, correlate with axonal pathology and chan...

## Key facts

- **NIH application ID:** 9701844
- **Project number:** 5I01RX000952-06
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** Matthew M. Harper
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2014-01-01 → 2019-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9701844

## Citation

> US National Institutes of Health, RePORTER application 9701844, Chronic effects of blast injury: analyses of Alzheimer related pathology (5I01RX000952-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9701844. Licensed CC0.

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