Contrast cTBI neuropathology to that of aging and wider neurodegenerative diseases

将 cTBI 神经病理学与衰老和更广泛的神经退行性疾病进行对比

• 批准号: 10024098
• 负责人: Douglas Hamilton Smith
• 金额: $ 9.02万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-30 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10024098
• 关键词: Admixture; Aging; Alzheimer' s Disease; Amyloid; Amyloid beta-Protein; Attention; Autopsy; Case Study; Characteristics; Chronic; Clinical; Cohort Studies; Complex; Consensus; Elements; Exposure to; Frontotemporal Lobar Degenerations; Goals; Heterogeneity; High Prevalence; Lesion; Lewy Body Disease; Link; Measurable; Methods; Nerve Degeneration; Neurocognitive; Neurodegenerative Disorders; Outcome; Pathology; Patients; Prevalence; Process; Recording of previous events; Reporting; Research Personnel; Research Project Grants; Risk; Standardization; Survivors; Syndrome; TBI Patients; TDP-43 aggregation; Techniques; Testing; Traumatic Brain Injury; aged; alpha synuclein; chronic traumatic encephalopathy; cohort; comorbidity; comparative; nervous system disorder; neuropathology; neuropsychiatry; tau Proteins

Research Project 2 SUMMARY There is growing concern over the association between traumatic brain injury (TBI) and progressive neurodegenerative changes, in particular those described as chronic traumatic encephalopathy (CTE). First recognized in boxers, it was not until later reports of similar pathologies in non-boxer athletes that the long-term consequences of TBI attracted widespread attention. Recent and preliminary consensus criteria propose CTE as a distinct neurodegenerative pathology, although the associated clinical consequences of this pathology remain unclear. Importantly, there is growing consensus that there is a high prevalence of comorbidity across neurodegenerative diseases including AD, Lewy body disease, and frontotemporal lobar degeneration. While, current reporting in CTE largely focuses on proposed “pathognomonic” tau pathologies, the heterogeneity of neurodegenerative disease neuropathology associated with chronic survival from TBI (cTBI) is not well described. Here we will evaluate the spectrum of neuropathologic change that is shared or unique between TBI- related neurodegeneration (TReND) versus other neurodegenerative diseases including Alzheimer’s disease (AD), Lewy body disease, and frontotemporal lobar degeneration. Specifically, by evaluating a neurodegenerative disease autopsy cohort of 275 cases, matched to the cTBI cohort studied in research project 1, we will examine for the presence and distribution of neuropathologies including Aβ amyloid, tau, α-synuclein and TDP-43 aggregates. Importantly, by examining a further cohort of 450 cases, we will also determine whether TReND pathology, like other neurodegenerative disease processes, can also be observed in neurodegenerative disease cases without any history of TBI.

研究项目2 摘要 创伤性脑损伤(TBI)与进展性脑损伤之间的关系日益受到关注 神经退行性改变，尤其是那些被描述为慢性创伤性脑病(CTE)的改变。第一 在拳击手中被发现，直到后来关于非拳击手运动员中类似病理的报道，长期的 创伤性脑损伤的后果引起了广泛关注。最近的和初步的共识标准建议CTE 作为一种独特的神经退行性病理，尽管这种病理的相关临床后果 目前仍不清楚。重要的是，越来越多的人达成共识，认为全世界的合并症发病率很高。 神经退行性疾病包括阿尔茨海默病、路易体病和额颞叶退行性变。而与此同时， 目前在CTE中的报道主要集中在所提出的“病因学”tau病理学上，即 脑外伤后慢性存活相关的神经退行性疾病(CTBI) 描述。在这里，我们将评估TBI之间共享或独特的神经病理变化的频谱- 相关神经变性(趋势)与包括阿尔茨海默病在内的其他神经退行性疾病 (AD)，路易体病，额颞叶变性。具体地说，通过评估 275例神经退行性疾病尸检队列，与研究项目中研究的cTBI队列匹配 1，我们将检查神经病理的存在和分布，包括Aβ淀粉样蛋白，tau，α突触核蛋白 和TDP-43聚合体。重要的是，通过进一步检查450例病例，我们还将确定 像其他神经退行性疾病过程一样，趋势病理也可以在神经退行性疾病中观察到。 无脑外伤病史的病例。