Are Tau Proteins in Blood and PET Images Related to Gulf War Illness and Risk of Comorbid Neurological Disorders?
Abstract
During the 1991 Gulf War (GW), U.S. Veterans were exposed to chemicals, pesticides, and nerve gas agents leading to chronic illness. This chronic disorder, Gulf War Illness (GWI), is characterized by cognitive decline, fatigue, and chronic pain that affects approximately a third of all Veterans who served in the GW. In our prior research studies, we identified higher levels of autoantibodies as an indirect measure of proteins that are produced by the immune system in response to foreign substances, in the blood of Veterans with GWI compared to healthy Veterans without GWI. These autoantibodies are related to a build-up of damaging proteins in the brain. These damaging proteins are hallmark indicators of neurological diseases and illnesses related to aging such as Alzheimer’s and Parkinson’s diseases. One specific protein that researchers have identified as related to neurological diseases is tau. In healthy brain cells or neurons, tau is normally a stabilizing structure. In Alzheimer s disease, however, abnormal chemical changes cause tau to detach and stick to other tau pieces, forming tangles that disrupt normal brain functioning. It has recently been discovered that these proteins exist in levels that are detectable in blood samples. The specific forms of these abnormal tau proteins that are associated with neurological disorders we are interested in include p-tau 181, p-tau 231, and p-tau 217. Our preliminary studies from a small sample of Veterans with GWI have indeed shown increased levels of total tau and p-tau 181 in their blood samples. Tau can also be visualized using brain scans such as positron emission tomography scans (PET scans). A PET scan involves the use of a tracer. The tracer then goes through the blood system and binds to the proteins in the brain and is detectable on pictures taken by the scanner. The brain scans are highly correlated to the blood tests but give a greater clinical picture of where the proteins are located within the brain. In this study, we will compare total tau levels and types of tau species called p-tau 181, p-tau 231, and p-tau 217 in larger numbers of stored blood samples from Veterans with GWI compared with healthy GW Veteran controls to verify our preliminary findings. Additionally, we will do tau PET scans on a smaller group of Veterans to see where the proteins are within the brain. In this study, we will determine whether Veterans with GWI have higher levels of tau proteins than healthy Veterans and whether the pattern or level of tau is associated with exposures during the war including pesticides, sarin nerve gas, anti-nerve gas pills, and history of mild traumatic brain injury in GW Veterans. Our study hypothesis (idea) is that GWI has led to early aging in Veterans, and we expect to see higher levels of tau in the blood samples of Veterans with GWI compared to the healthy Veterans. We think that more nervous system damage and accelerated aging processes in GWI is related to the higher levels of total tau and p-tau proteins. We think this will be identified in the blood of GW Veterans with GWI, as determined by Kansas GWI criteria, compared with healthy control Veterans from the Boston Biorepository and Integrative Network (BBRAIN) for GWI cohort of stored samples which is also led by Dr. Kimberly Sullivan. We also hypothesize that Veterans with GWI will have more tau in areas of the brain that are associated with cognition and memory. The results from this study may help Veterans with GWI in multiple ways. First, our study may change the way GWI and other similar disorders are diagnosed by using a simple blood test for immune system activation of brain proteins. Second, it may change the way that GWI and other similar disorders are treated if it is shown that a particular pattern of brain markers are associated with early aging processes such as Alzheimer’s disease. This could result in utilizing currently available U.S. Food and Drug Administration (FDA)-app
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210329
Entities
People
- Kimberly Sullivan
Organizations
- Boston University Medical Campus
- United States Army