Twenty-seven years have passed since the end of the 1990-1991 Gulf War (GW). The youngest of the approximately 700,000 Gulf War Veterans (GWV) who served in that war are now 45 years old and about half are age 55 and older. In addition to the usual age-related comorbidities, as many as one third of the men and women who served in Operations Desert Shield and Desert Storm during the GW have experienced chronic, multisystem illnesses collectively known as Gulf War Illness (GWI). Prevalent complaints are central nervous system (CNS) dysfunction, musculoskeletal pain, fatigue, respiratory symptoms, gastrointestinal issues, immunological dysfunction, and skin problems. Furthermore, GWVs have been shown to have elevated rates of brain cancer, amyotrophic lateral sclerosis (ALS), stroke, migraine headaches, neuralgia and neuritis. Additionally, recent anecdotal evidence from our group and other Boston colleagues suggests that mild traumatic brain injuries (mTBI) may be more prevalent in GWVs than previously appreciated, which may increase risk for long term sequelae such as chronic traumatic encephalopathy (CTE) and dementia. Neurobehavioral findings include memory problems, executive system deficits, slowed motor and processing speeds, sustained attention deficits, reduced visuospatial skills and psychomotor dysfunction. Given the spectrum of deficits noted above, combined with evidence of structural and functional abnormalities on neuroimaging, it is likely that neuropathological changes also occur in GWI. Several environmental exposures have been implicated as potential contributors to GWI including exposure to acetylcholinesterase (AChE) inhibitors such as pyridostigmine bromide (PB; anti-nerve gas pills) and organophosphate (OP) pesticides/nerve agents (e.g., sarin/cyclosarin). Given the issues raised above, there is a critical need for a GWI CNS postmortem tissue biorepository that will conduct extensive ante mortem longitudinal assessments on GWVs enrolled prior to their passing. Our first specific aim is to continue and enhance the Gulf War Veterans’ Illnesses Biorepository (GWVIB) as a national resource to support research on the etiology and pathogenesis of GWI and associated neurological disorders, and our second aim is to leverage the GWVIB as a value-added resource for all GWI research studies by co-enrolling GWVS from these cohorts and providing long term follow up and brain banking. Well-characterized postmortem CNS tissue when combined with antemortem health data and biological assessments (such as ApoE genotype and serum PON1 activity) will be invaluable to advance research on GWI. The GWVIB is a multi-site collaboration among VA Boston Healthcare System (VABHS) and the Southern Arizona VA Healthcare System (SAVAHCS). The GWVIB will utilize strengths across the Boston and Tucson sites in enrollment, tissue collection, processing, storage, neuropathological diagnosis, medical informatics and data management. VABHS will serve as the operations/data coordinating center and conduct the neuropathological diagnostic analyses, with SAVAHCS contributing expertise in CNS tissue processing and storage. SAVAHCS will also coordinate CNS tissue distribution. Notable enhancements to be initiated in this funding cycle are the utilization of an active recruitment of GWVs with brain cancer and age-related neurodegenerative disorders (along with our ongoing recruitment of GWVs in general) via our collaboration with VA neuro-oncology and neurology clinics. Our recently developed collaboration with new large scale national GWI studies will provide new cohorts of GWVs interested in participating in research, which has been shown to improve recruitment success for brain donation. The GWVIB will partner with these GWI studies to form collaborative GWI research networks to co- enroll GWVs to enhance the overall VA GWI research portfolio at a relatively low incremental cost.

Up to one third of the 700,000 service members who served in Operations Desert Shield/Desert Storm during the 1990-1991 Gulf War (GW) developed a chronic illness called Gulf War Illness (GWI). Many affected veterans have problems with thinking and memory and brain scans have shown abnormal brain structure. The cause of GWI is not known but it may be related to exposure to environmental toxins. GW veterans may also be at increased risk for progressive brain problems such as Alzheimer’s disease due to accelerated brain aging and long-term effects of brain injuries. Scientists in the field agree that more studies using human brain tissue obtained after death are vital to accelerate research on GWI. To meet this critical need we established and will continue to enhance the Gulf War Veterans’ Illnesses Biorepository (GWVIB) as an essential resource to support research on the causes of GWI and the development of effective treatments for those affected by this debilitating illness.