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

世贸中心老龄化响应人员中阿尔茨海默病神经病理学的负担和变化

基本信息

批准号：
10371245
负责人：
SEAN CLOUSTON
金额：
$ 79.38万
依托单位：
STATE UNIVERSITY NEW YORK STONY BROOK
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-03-15 至 2026-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10371245
关键词：
Age Aging Alzheimer&apos s Disease Alzheimer&apos s disease related dementia American Amyloid Amyloid beta-Protein Amyloid deposition Biological Markers Blood Brain Brain imaging Case-Control Studies Chronic Post Traumatic Stress Disorder Clinical Clinical Trials Cognitive Cognitive aging Data Deposition Diagnosis Disease Dust Early Onset Alzheimer Disease Education Ethnic Origin Etiology Event Exposure to Feasibility Studies Funding Health Impaired cognition Incidence Individual Inflammatory Life Ligands Light Link Magnetic Resonance Magnetic Resonance Imaging Measures Medical Minority Women Molecular Monitor Nature Nerve Degeneration Neurobehavioral Manifestations Neurocognitive Neurodegenerative Disorders Occupations Olfactory Cortex Pathogenesis Patients Pattern Peripheral Physical Function Pituitary Gland Plasma Population Positron-Emission Tomography Post-Traumatic Stress Disorders Prognosis Prospective Studies Proteins Proteomics Protocols documentation Quality of life Race Recording of previous events Recovery Research Severities Site Staging Stressful Event Symptoms Tauopathies Temporal Lobe Thick Time Visit Woman age related aged base blood-based biomarker cognitive testing cohort critical period entorhinal cortex expectation experience follow-up imaging biomarker improved in vivo longitudinal positron emission tomography men middle age mild cognitive impairment neurofilament neuroimaging neuroinflammation neuropathology operation particle physically handicapped programs recruit response sex stressor symptomatology tau Proteins treatment response

项目摘要

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.

抽象的世界贸易中心（WTC）响应者在救援时暴露于微小的灰尘颗粒的混合以及2001年9月11日之后的WTC的恢复工作。大量数量继续遭受后创伤应激障碍（PTSD）是由于他们的经验。这些可能改变了他们的期望随着年龄的增长。我们的团队询问了早期认知衰老迹象的潜力，并已确定轻度认知障碍（MCI）的预期燃烧高于预期的燃烧，令人惊讶地改变了身体功能在身体残疾和神经退行性疾病中常见的局限性（PFL）。考虑到大小和围绕9/11的事件的规模以及年轻平民中的暴露水平，先前的研究是不足以确定WTC响应者队列中MCI的发病机理。我们建议MCI正在出现早期，因为PTSD引起神经炎症反应，从而增加了垂直腺的激活导致阿尔茨海默氏病神经病理学增加。我们建议进行大型纵向宠物/MRI 使用两种验证正电子发射断层扫描（PET）的120个医学健康的WTC响应者的研究配体（[11C] -PIB测量β-淀粉样蛋白和[18F] -Flortaucipir，以测量tauopathy）。详细的认知测试将有助于确定认知功能障碍的水平。同时结构MRI将用于测量神经变性的程度。蛋白质组学分析将完成以跟踪变化并验证监视该人群中的生物标志物计划。这项研究之所以及时，是因为我们处于关键时期神经病理学仍在出现。