Neuropathology of CTE and Delayed Effects of TBI: Toward In-Vivo Diagnostics

CTE 的神经病理学和 TBI 的延迟效应：走向体内诊断

基本信息

批准号：
9212693
负责人：
Kristen Dams-O'Connor
金额：
$ 147.95万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-01-01 至 2019-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9212693
关键词：
Adult Age Age of Onset Alzheimer&apos s Disease Autopsy Base of the Brain Behavioral Behavioral Genetics Biological Markers Biological Models Blast Cell Brain Brain Injuries Cessation of life Characteristics Classification Clinical Clinical Data Cognitive Communities Consensus Consensus Development Consent Craniocerebral Trauma Data Data Collection Data Sources Databases Dementia Development Diagnosis Diagnostic Enrollment Ensure Epidemiology Evaluation Genetic Genomics Goals Health Image Incidence Individual Knowledge Late Effects Lead Lesion Life Link Long-Term Effects MRI Scans Magnetic Resonance Imaging Manufactured football Medical Methods Military Personnel Modality Nerve Degeneration Outcome Parkinson Disease Participant Pathologic Pathology Pattern Population Prevalence Procedures Process Prospective cohort study Protocols documentation Public Health Recording of previous events Research Research Design Research Infrastructure Research Personnel Resolution Resources Risk Factors Role Sampling Selection Bias Signs and Symptoms Site Specimen Statistical Methods Subgroup Survivors Tauopathies Techniques Texas Time Tissues Trauma Traumatic Brain Injury United States United States National Institutes of Health Universities Work accurate diagnosis aging brain associated symptom base chronic traumatic encephalopathy clinical diagnostics cohort design experience improved in vivo multidisciplinary neurobehavioral neuroimaging neuropathology population based programs prospective public health relevance tau Proteins tool validation studies

项目摘要

DESCRIPTION (provided by applicant): The proposed project, "Neuropathology of CTE and Late Effects of TBI: Toward In-Vivo Diagnostics" is a multi- center and multi-disciplinary study designed to dramatically increase our understanding of chronic traumatic encephalopathy (CTE) and other late effects of traumatic brain injury (TBI). TBI is a major public health concern in the US, as the current prevalence of TBI in the US is unprecedented. Some TBI survivors experience particularly poor outcomes as they age; these include accelerated cognitive and health decline, dementia, and in some cases, CTE. CTE is thought to be a tauopathy but has been described only in convenience samples of people with repetitive head trauma. CTE is incompletely described in individuals with mild, moderate and severe TBI. The population incidence and prevalence, risk factors, and causal role of multifocal tauopathy on associated symptoms are unknown. Overlapping clinical features, postmortem pathologies and patterns of involvement exist in TBI, CTE, and Alzheimer's disease pose challenges to accurate diagnosis. Premortem diagnosis of CTE is currently impossible. The neuropathological consequences of single mild or moderate-severe TBI and its relationship with CTE and known dementias are unclear. The proposed project will leverage extensive resources from an ongoing population-based prospective cohort study of brain aging (Adult Changes in Thought; ACT, n=2,305) which includes excellent medical, behavioral, and genetic characterization of a cohort (20% of whom have a history of mild-moderate TBI) in addition to state-of-the-art neuropathology workup upon death. Neuropathological study of TBI effects can begin immediately in the existing ACT autopsy sample (n=489, 20% with TBI exposure). Additional cohorts of TBI- exposed individuals will come from the Brain Injury Research Center at Mount Sinai (n=150 individuals with moderate-severe TBI), the University of Texas Southwestern (n=50 retired boxers with repetitive TBI exposure), and the National Football League (n=76 retired players with repetitive TBI exposure). All participants in the proposed study (ACT and other sites) will undergo uniform harmonized neurobehavioral assessment (chosen to maximize correspondence with existing large-scale TBI and dementia studies), MRI scan, and genomic analysis. Those individuals who expire during the course of the study will undergo ex-vivo neuroimaging and extensive neuropathological exam using state-of-the-art techniques (such as Histelide) designed to quantify tau and A� in whole brain specimens. Only by examining postmortem pathology in a sample of individuals with varying levels of TBI exposure who are well characterized during life (as proposed herein) can postmortem pathology facilitate identification of in-vivo biomarkers that can act as diagnostic tools. This project represents the most systematic and scientifically rigorous effort to date to develop a more complete understanding of the long-term clinical and neuropathological sequelae of single and multiple TBI.

描述（由适用提供）：拟议的项目，“ CTE的神经病理学和TBI的后期影响：迈向体内诊断”是一项多中心和多学科的研究，旨在显着增加我们对慢性创伤性脑病（CTE）的理解（CTE）和其他大脑损伤的其他后期影响（TBI）。 TBI是公共卫生的主要关注我们，因为美国当前的TBI患病率是前所未有的。随着年龄的增长，一些TBI生存的结果特别差。这些包括加速的认知和健康下降，痴呆，在某些情况下，CTE。 CTE被认为是一种tauopathy，但仅以重复性头部创伤的人的便利样本进行了描述。 CTE在患有轻度，中度和重度TBI的个体中未完全描述。多焦点tauopathy对相关症状的人口发生率和流行率，危险因素和因果关系的作用尚不清楚。在TBI，CTE和阿尔茨海默氏病中存在重叠的临床特征，死后病理和参与模式，对准确的诊断构成了挑战。目前不可能使用CTE的Premortem诊断。单个轻度或中度重度TBI及其与CTE和已知痴呆症的关系的神经病理学后果尚不清楚。拟议的项目将利用基于人群的脑老化前瞻性队列研究（成人思想变化； ACT，n = 2,305）的广泛资源，其中包括出色的医学，行为和遗传表征（其中20％的同类均具有轻度敏感性TBI的历史），此外，除了对死亡的先行神经病理学的工作外，还包括其他的。 TBI效应的神经病理学研究可以立即开始在现有的ACT尸检样本中（n = 489，20％带有TBI暴露）。其他人群暴露的人将来自西奈山的脑损伤研究中心（n = 150名中度重度TBI的人），得克萨斯州西南大学（n = 50个退休的拳击手，具有重复性的TBI暴露）和国家橄榄球联盟（n = 76个退休的球员，都有重复性TBI TBI）。拟议研究的所有参与者（ACT和其他站点）都将接受统一的统一神经行为评估（选择以最大程度地与现有的大规模TBI和痴呆症研究最大化），MRI扫描和基因组分析。那些在研究过程中到期的人将使用最先进的技术（例如HisteLide）进行外神经影像学和广泛的神经病理学检查（例如Histelide），旨在量化整个大脑标本中的TAU和A。仅通过检查具有不同水平的TBI暴露的个体样本中的死后病理学，这些样本在生活中表现得很好（如本文所建议的），可以在现年病理学后病理学准备可以用作诊断工具的体内生物标志物的鉴定。该项目代表了迄今为止最系统，最严格的努力，以对单个和多个TBI的长期临床和神经病理后遗症有了更完整的了解。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Bringing posttraumatic sleep-wake disorders out of the dark.

将创伤后睡眠觉醒障碍带出黑暗。

DOI：
10.1212/wnl.0000000000002710
发表时间：
2016
期刊：
Neurology
影响因子：
9.9
作者：
Edlow,BrianL;Lammers,GertJan
通讯作者：
Lammers,GertJan

Intimate Partner Violence and Other Trauma Exposures in Females With Traumatic Brain Injury.

患有创伤性脑损伤的女性遭受亲密伴侣暴力和其他创伤。

DOI：
10.1089/neu.2023.0225
发表时间：
2024
期刊：
Journal of neurotrauma
影响因子：
4.2
作者：
deSouza,NicolaL;Kumar,RajG;Pruyser,Ariel;Blunt,EmilyE;Sanders,William;Meydan,Anogue;Lawrence,Phoebe;Venkatesan,UmeshM;MacDonald,ChristineL;Hoffman,JeanneM;Bodien,YelenaG;Edlow,BrianL;Dams-O'Connor,Kristen
通讯作者：
Dams-O'Connor,Kristen