Determining the Role of Tau and Amyloid in Chronic Symptoms and Deficits in Military Personnel Following TBIs Through PET Imaging
Abstract
Background: Military personnel who deploy to combat are at high risk for traumatic brain injuries (TBIs). Those who suffer a TBI are at higher risk to develop chronic behavioral and neurological symptoms and deficits. These risks are highest in those military personnel/veterans who sustain multiple TBIs, or more TBIs. Mechanisms underlying these symptoms and deficits remain unclear. There is a reported link between TBIs and Alzheimer s disease (AD) and AD-like dementia (ADRD), but this relationship remains questionable. It may be that in some individuals, a TBI initiates a neurodegenerative process that shares pathological features with AD and ADRD. These risks may include the presence of tau tangles and amyloid-beta (Aß) plaques in the brain. Studies using positron emission tomography (PET), a neuroimaging method to visualize aggregation of proteins in the brain, report that tau neurofibrillary tangles (NFT) are present in athletes with multiple concussions. There is also evidence that even a single TBI increases the risk for Aß plaques. Yet, these tau and Aß PET findings are not present in all TBI patients, and their role in chronic symptoms following a TBI remains largely unknown. Determining the presence of Aß plaques and tau NFTs in younger cohorts of military personnel and veterans and their relation to chronic behavioral and neurological symptoms is important. Aß plaques are linked to neuropsychological deficits and have been shown to predict conversion from mild cognitive impairment (MCI) to AD/ADRD in older civilian samples, but their contribution to symptoms and deficits in is younger individuals with TBIs remains unknown. Previously, we reported greater tau NFTs were present in athletes with multiple concussions and behavioral and neurological symptoms. Our group has also shown proteins in the blood relate to greater symptoms of post-traumatic stress disorder and post-concussive disorder, as well as greater neurocognitive deficits. Proteins implicated in these symptoms and deficits included tau, Aß40/42, and cytokines. These findings have implications to understanding chronic symptoms in military personnel, as conversion from MCI to AD/ADRD has been linked to elevations of these same proteins. In the proposed study, we will use PET with ligands specific to amyloid and tau to determine if a TBI results in tau NFTs and Aß plaques, 10-years following a TBI, in a young military cohort. We will then examine if these PET changes have clinical implications 10-years post TBI. Finally, we will evaluate changes in blood-based biomarkers implicated in AD to determine if these peripheral markers are related to neuronal changes. Results of these investigations will determine if there is an increased risk for AD-like pathology following a TBI in military personnel and if PET findings have clinical implications to military personnel/veterans. We hypothesize that: (a) military personnel with a TBI will have higher rates of Aß plaque and tau NFT formation 10 years following injury compared to controls without TBI; (b) military personnel with multiple TBIs, greater severity of TBI, and those with more neuropsycholgical deficits and clinical symptoms, will be more likely to have Aß plaques and tau NFTs, and (c) changes in biomarkers over will predict those military personnel with Aß plaque and tau NFT formation 10 years following the TBI. Specific Aims: 1: Determine if Aß plaques and tau NFTs (as measured by PET) differ in military personnel 10 years following a TBI, compared to matched military controls without TBIs. 2: Determine if clinical symptoms, TBI characteristics (i.e., number and severity of TBI), neuropsychological functioning, whole brain volume loss, and white matter degradation is associated with Aß plaques and tau NFTs 10 years following a TBI 3: Determine if changes in blood biomarkers (tau, p-tau, amyloid precursor protein, Aß 40/42, cytokines, vascular endothelial growth factor) over time up until 10 yea
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jul 03, 2019
- Source ID
- W81XWH1810691
Entities
People
- Jessica Gill
Organizations
- Henry M. Jackson Foundation for the Advancement of Military Medicine
- United States Army