# Traumatic Brain Injury and Repetitive Head Impacts: Contributions to AD/ADRD and CTE Neuropathology and Resulting Clinical Syndromes

> **NIH NIH U54** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2022 · $1,989,941

## Abstract

Individuals who experience traumatic brain injury (TBI) are at increased risk for developing dementia and
parkinsonism later in life. Exposure to repetitive head impacts (RHI) from contact sports and military service is
also associated with a tau-based neurodegeneration, chronic traumatic encephalopathy (CTE). Our small case
studies indicate that the neuropathological substrate of TBI-related neurodegeneration is a heterogeneous
condition with varying degrees of beta-amyloid (Aß), phosphorylated tau (ptau), pTDP-43, and alpha-synuclein
pathologies that does not conform to conventional Alzheimer's disease (AD) or AD related dementias (ADRD).
Our studies also suggest that other pathologies, including gray and white matter atrophy, vascular pathology,
neuronal, axonal and myelin loss, astrocytosis, and neuroinflammation contribute to neurodegeneration after TBI
and RHI. Moreover, it is increasingly recognized that the type, frequency and severity of TBI or RHI and other
genetic and non-genetic factors exert striking influence on the long-term outcome. TBI and RHI have not been
well studied in brain bank cohorts, subsequently, the contribution of TBI and RHI to AD, ADRD, CTE and other
pathologies is not known. There is a critical unmet need to determine the relationship of TBI and RHI to AD,
ADRD, CTE and other pathologies, to understand the neuropathological phenotype of TBI, to determine the
prevalence of TBI-related neurodegeneration and CTE in brain bank cohorts, and to determine the relationship
of TBI and RHI to cognitive decline and parkinsonism. To accomplish our goals, we will leverage the
infrastructure of our successful Understanding Neurological Injury and Traumatic Encephalopathy (UNITE) study
(U01NS086659, R01AG057902) and our collaboration with Mount Sinai (U01NS086625). We will harmonize 8
novel brain banks: 6 at Boston University (BU) and 2 at Icahn School of Medicine at Mount Sinai (ISMMS). In
this proposal, we will examine the association of RHI and TBI with AD, ADRD, CTE neuropathology and other
pathologies and investigate genetic and non-genetic modifiers of these effects. The overarching hypotheses
are: RHI and TBI will have distinct associations with AD, ADRD, CTE and other pathologies; these effects will
be modified by genetic (e.g., APOE ε4, TMEM106b) and non-genetic factors (e.g., age of first exposure to RHI
 )
and TBI, age, cardiovascular disease, resistance, among other RHI/TBI characteristics and demographic,
lifestyle, and medical histories ; and these pathologies will have direct associations with clinical outcomes of
dementia and parkinsonism. This U54 will develop the largest brain donor cohort with well-characterized histories
of RHI and TBI across the severity spectrum. This project will advance knowledge on the specific risks for the
pathological development of AD, ADRD, CTE and other degenerative pathologies after RHI and TBI, establish
the neuropathological features of TBI-related neurodegeneration, and determin...

## Key facts

- **NIH application ID:** 10460261
- **Project number:** 5U54NS115266-04
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Ann C. McKee
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,989,941
- **Award type:** 5
- **Project period:** 2019-09-30 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10460261

## Citation

> US National Institutes of Health, RePORTER application 10460261, Traumatic Brain Injury and Repetitive Head Impacts: Contributions to AD/ADRD and CTE Neuropathology and Resulting Clinical Syndromes (5U54NS115266-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10460261. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*