# The neuropathology of mild traumatic brain injury in Alzheimer's disease

> **NIH VA I01** · EDITH NOURSE  ROGERS MEMORIAL VETERANS HOSPITAL · 2024 · —

## Abstract

Repetitive head impacts (RHI) are a form of mild traumatic brain injury that can lead to severe cognitive and
behavioral symptoms and the progressive neurodegeneration of chronic traumatic encephalopathy (CTE).
Trauma is also a known risk factor for Alzheimer disease (AD), and we hypothesize that a prolonged period of
RHI can play a causative role in the development of AD as well as CTE. In addition, cerebrovascular disease is
a well-known contributor to cognitive impairment; however, the role of vascular changes in the development of
CTE and AD pathology are not well understood. Cerebrovascular integrity is critical for proper metabolism and
perfusion of the brain. Compliance of large cerebral arteries allows these arteries to dampen the pulsatile
pressure and protect the microcirculation and blood brain barrier from damage. Thus, cerebrovascular
dysfunction can have detrimental impacts on the brain, including increased susceptibility to pulse pressure,
blood brain barrier breakdown and ineffective clearance of tau pathology, beta-amyloid, and other toxic
metabolites. The overall goal of this project is to determine whether RHI is associated with
cerebrovascular remodeling and the progression of CTE and compare to the role of cerebrovascular
remodeling in AD.
Building upon our multidisciplinary expertise in vascular mechanobiology, precision mass spectrometry,
advanced optical imaging, immunohistochemistry, vascular biology and neuropathology of CTE and AD, we
will test this hypothesis in three aims: Aim 1) to determine cerebrovascular remodeling (biomechanical,
structural, and compositional changes) in the frontal lobe in CTE; Aim 2) to determine the association between
cerebrovascular remodeling and CTE and AD pathological changes; and Aim 3) to examine the association
between cerebrovascular remodeling and RHI history and antemortem cognitive status. We will use no or low
atherosclerotic cerebrovascular and brain tissue from 80 age- and sex-matched brain donors from the NIH and
VA-funded BU Alzheimer Disease & CTE Research Center with 1) no RHI history and no pathology, 2) RHI
history with no CTE, 3) low CTE pathology, and 4) high CTE pathology. These brain donors have undergone
medical review and informants are given extensive structured interview/questionnaires using modified
questions from the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set (UDS), including
postmortem assessments of cognitive functioning (including memory, language, attention, executive function
and visuospatial function).
This proposal is designed to leverage existing resources to make new discoveries. The matched and parallel
studies of cerebral vessels and brain tissue will provide new understandings of the temporal development of
cerebrovascular remodeling in CTE. Understanding the role of vascular remodeling in CTE may lead to the
discovery of new treatment options and directions for interventions to stave off cognitive impairment in our
military Vete...

## Key facts

- **NIH application ID:** 10829795
- **Project number:** 5I01BX005933-10
- **Recipient organization:** EDITH NOURSE  ROGERS MEMORIAL VETERANS HOSPITAL
- **Principal Investigator:** Thor Stein
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2013-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10829795

## Citation

> US National Institutes of Health, RePORTER application 10829795, The neuropathology of mild traumatic brain injury in Alzheimer's disease (5I01BX005933-10). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10829795. Licensed CC0.

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