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（由申请人提供）：拟议项目“CTE 的神经病理学和 TBI 的晚期影响：迈向体内诊断”是一项多中心、多学科研究，旨在显着增进我们对慢性创伤性脑病 (CTE) 的了解以及创伤性脑损伤 (TBI) 的其他后期影响是一个主要的公共卫生问题。在美国，目前 TBI 的患病率是前所未有的，一些 TBI 幸存者随着年龄的增长，会出现特别糟糕的结果；其中包括认知能力和健康状况加速下降、痴呆，在某些情况下，CTE 被认为是一种 tau 蛋白病。仅在重复性头部外伤患者的方便样本中进行了描述。在患有轻度、中度和重度 TBI 的个体中，CTE 的描述并不完整。多灶性 tau 病的人群发病率和患病率、危险因素以及相关临床症状的因果作用尚不清楚。 TBI、CTE 和阿尔茨海默病的特征、死后病理和参与模式对 CTE 的准确诊断目前是不可能的。单一轻度或中重度 TBI 的神经病理学后果及其与 CTE 和已知痴呆的关系。拟议的项目将利用正在进行的基于人群的大脑衰老前瞻性队列研究（成人思维变化；ACT，n=2,305）的广泛资源，其中包括出色的医学、行为和遗传研究。除了死亡时最先进的神经病理学检查之外，还可以在现有的 ACT 尸检样本中立即开始对队列进行表征（其中 20% 有轻度至中度 TBI 病史）。 489 人，其中 20% 患有 TBI 暴露），其他 TBI 暴露人群将来自西奈山脑损伤研究中心（n = 150 名中重度 TBI 患者）。德克萨斯大学西南大学（n = 50 名重复接触过 TBI 的退役拳击手）和国家橄榄球联盟（n = 76 名重复接触过 TBI 的退休运动员）拟议研究（ACT 和其他地点）的所有参与者都将接受统一的协调神经行为测试。评估（选择最大化与现有大规模 TBI 和痴呆研究的一致性）、MRI 扫描和基因组分析。在研究过程中过期的个体将接受离体神经成像和广泛的神经病理学检查。最先进的技术（例如 Histelide）旨在量化全脑标本中的 tau 和 A�，仅通过检查生前具有不同 TBI 暴露水平的个体样本的死后病理学（如提议的）。死后病理学可以促进体内生物标志物的识别，这些生物标志物可以作为诊断工具。该项目代表了迄今为止最系统和科学严谨的努力，旨在更全面地了解单一和多重的长期临床和神经病理学后遗症。创伤性脑损伤。

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