Burden and change in Alzheimers disease neuropathology in aging World Trade Center responders

摘要 世界贸易中心（WTC）的救援人员在参与救援时暴露在微小的尘埃颗粒中 2001年9月11日之后，世贸中心的重建工作。许多人继续遭受后... 创伤性应激障碍（PTSD）是他们经历的结果。这些可能改变了他们的预期 健康随着年龄的增长。我们的团队已经研究了认知老化早期迹象的可能性， 轻度认知障碍（MCI）的负担高于预期，令人惊讶的是， 限制（PFL）常见于身体残疾和神经退行性疾病。鉴于其规模和 围绕9/11事件的事件规模和年轻平民人口的暴露水平，先前的研究是 不足以确定WTC应答者队列中MCI的发病机制。我们认为MCI正在产生 因为创伤后应激障碍会引起神经炎症反应，导致脑垂体激活增加 导致阿尔茨海默病神经病理学的增加。我们建议进行一个大型纵向PET/MRI 使用两种经过充分验证的正电子发射断层扫描（PET）对120名医学上健康的WTC应答者进行研究 配体（[11 C]-PiB测量β-淀粉样蛋白，[18 F]-Flortaucipir测量tau蛋白病）。详细认知测试 将有助于确定认知功能障碍的程度将使用同步结构MRI测量 神经变性的程度。将完成蛋白质组学分析，以跟踪变化并验证监测 在这个人群中进行生物标志物的研究。这项研究是及时的，因为我们正处于一个关键时期， 神经病理学仍在兴起。

Abstract World Trade Center (WTC) responders were exposed to a mix of tiny dust particles as they participated in rescue and recovery efforts at the WTC in the aftermath of 9/11/2001. A significant number continue to suffer from Post- Traumatic Stress Disorder (PTSD) as a result of their experiences. These may have changed their expectations of health as they age. Our team has interrogated the potential for early signs of cognitive aging and has identified higher than expected burden of mild cognitive impairment (MCI) and, surprisingly, changes to physical functional limitations (PFL) common in both physical disability and in neurodegenerative disease. Given the magnitude and scale of events surrounding 9/11 and the level of exposure within a young civilian population, prior studies are insufficient in determining the pathogenesis of MCI in the WTC responder cohort. We propose that MCI is arising early because PTSD causes a neuroinflammatory response resulting in increased activation of the pituitary gland resulting in increased Alzheimer’s disease neuropathology. We propose to conduct a large longitudinal PET/MRI study of 120 medically-healthy WTC responders using two well-validated positron emission tomography (PET) ligands ([11C]-PiB to measure β-amyloid, and [18F]-Flortaucipir to measure tauopathy). Detailed cognitive testing will help to determine the level of cognitive dysfunction. Simultaneous structural MRI will be used to measure the extent of neurodegeneration. Proteomic analyses will be completed to track changes and to validate a monitoring program for biomarkers in this population. This study is timely because we are in a critical period when neuropathology is still emerging.