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

摘要 世贸中心(WTC)的救援人员在参与救援时暴露在微小尘埃颗粒的混合物中 9/11/2001事件后，世贸中心的重建工作。相当多的人继续遭受后遗症- 由于他们的经历而导致的创伤应激障碍(PTSD)。这些可能改变了他们的预期 随着年龄的增长，他们的健康状况也会有所改善。我们的团队已经询问了认知老化的早期迹象的可能性，并发现 轻度认知障碍(MCI)的负担高于预期，令人惊讶的是，身体功能的变化 限制(PFL)在身体残疾和神经退行性疾病中都很常见。考虑到大小和 9/11事件的规模和年轻平民人口中的暴露水平，先前的研究是 在WTC应答者队列中不能确定MCI的发病机制。我们认为MCI正在兴起 早期是因为创伤后应激障碍会引起神经炎性反应，导致脑下垂体的激活。 导致阿尔茨海默病神经病理加重。我们建议进行大型纵向正电子发射计算机断层扫描 两种有效的正电子发射断层扫描(PET)对120名医疗健康WTC应答者的研究 配体([11C]-PIB用于测量β-淀粉样蛋白，[18F]-Flortaucipir用于测量转位症)。详细的认知测试 将有助于确定认知功能障碍的程度。同步结构磁共振将被用来测量 神经变性的程度。将完成蛋白质组分析以跟踪变化并验证监测 为这一人群中的生物标志物制定计划。这项研究是及时的，因为我们正处于一个关键时期， 神经病理学仍处于初级阶段。

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.