Impact of Traumatic Brain Injury on Tauopathy-Induced Synaptotoxicity: Implications for Alzheimers Disease and Related Dementias
Abstract
Dementia is a chronic condition characterized by a progressive cognitive decline that leads to functional disability. Alzheimer’s disease is the most common cause of dementia in the elderly. Traumatic brain injury (TBI) is an important risk factor for the development of AD (AD). In fact, studies have shown that a single moderate to severe head injury can lead to increased presence in the brain of the two hallmark signs of AD, amyloid-beta plaques and neurofibrillary tangles. Although TBI has been recognized as a leading cause of death and disability, controversy remains about the long-term consequences. This study will explore the link between TBI and AD pathology, in particular, the role of neurofibrillary tangles, since the mechanisms underlying the risk of developing AD pathology following TBI injury are poorly understood. Our goal is to understand how brain injury triggers the overproduction of the toxic forms of the neurofibrillary tangle protein, named tau, and determine if TBI triggers the same changes in tau that occur as dementia develops. Further, evidence suggests that AD is primarily a disease of dysfunctional synapses, the brain structure that permits neurons to pass electrical or chemical signals to each other. Therefore, we will also determine the role tau in synaptic dysfunction long-term after brain injury. After AD, frontotemporal dementia (FTD) is the second most common cause of dementia with onset before 65 years of age, and recently TBI has also been suggested to be a risk factor for FTD, which encompasses several types of dementia. Since toxic forms of tau protein also play a role in certain types of FTD, this work is also relevant for these patients. Understanding how TBI may contribute to the development of dementia, to direct efforts for prevention and treatment, may be one of the most important challenges facing public health today, particularly for Veterans, combat Soldiers, athletes, and those who may suffer from future TBI, since the number of patients suffering from AD and other dementias is expected to rise significantly over the next few decades.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910698
Entities
People
- Kelly Stauch
Organizations
- United States Army
- University of Nebraska Medical Center