Phosphorylation Tau Profile of Veterans with TBI
Abstract
Objective: Active military Veterans remain a susceptible population for exposure to traumatic brain injury (TBI) and also have a higher rate of developing Alzheimer’s disease (AD). The Defense and Veterans Brain Injury Center reported 434,618 military personnel sustained a TBI since 2000. Injury to the head is known to increase the risk of an individual for developing a classification of neurological disorders referred to as tauopathies. These disorders share one primary pathological marker that is based on the abnormal malformation of the tau protein. Chronic traumatic encephalopathy is one such example that has been observed in postmortem studies of sports related concussion. However, the types of head injuries sustained by Veterans are different, and recent work has ruled this tauopathy out as a likely source for the cognitive and brain related decline that is observed in this population. AD is another neurological disorder that is classified as a tauopathy, and the higher incidence rate of its presence in this cohort makes it a likely candidate for changes in mental status for these individuals. However, prior work has failed to show signs of early biomarker changes that are typically associate with Alzheimer’s disease. Therefore, we posit that TBI-induced AD in this cohort is an atypical variant that is more tau-oriented, and by studying the tau changes more closely, we can identify Veterans with a history of TBI who are at risk for developing AD (Focus Area 2). Patient Benefits: The primary focus of care for this proposal are future active or retired military personnel who sustained a TBI and are potentially at risk for future cognitive decline. Currently, there are no biomarkers available for predicting an AD prognosis in military Veterans beyond standard approaches available to the general public despite an increased incidence rate. However, this tau-oriented focus is not only limited to military Veterans, as the general public are also exposed to head-related injuries, and this work can possibly be translatable to a more generalizable population. Potential Benefits/Risks: Part of our proposal is to reassess the validity of acquiring this tau biomarker in the blood compared to a lumbar puncture. If this metric can reliably be acquired in the blood as prior work would suggest, then this would make this a financially feasible way to assess the risk of an individual with very little burden. In the case of Veterans, theses data could be acquired during their deployment or at home to carefully monitor their risk assessment by their personal physician. To our knowledge, this process would not expose the individuals to any unnecessary risks or deleterious consequences. Clinical Projected Timeline: There are several benefits to our approach that would expedite the process for this biomarker to being clinically relevant. The tau changes that we focus on for this proposal have already been established as part of an AD-related mechanism but has not been modeled in the way we propose here. Additionally, the cohort that we will be testing is based on human samples and is therefore closer to a clinical application than animal work. Although the particular tau changes that we focus on for this grant are not currently used in a clinical setting, similar biomarkers currently are. Scientific Contributions: The focus of this proposal is testing a unique variant of AD that has not previously been conceptualized. The findings from this project can reshape how we think about Alzheimer Disease and thereby affect drug treatment strategies. Additionally, this would establish a mechanistic link between head injury and AD that has previously only been alluded to but not well described. Most importantly, it would provide a biomarker for identifying at risk individuals at early stages of the disease as well as a potential outcome variable for clinical trials. Impact on Veteran Health: Veterans are already at
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310116
Entities
People
- Jeremy Strain
Organizations
- United States Army
- Washington University in St. Louis