Characterize the extent, distribution and range of pathologies contributing to TReND in cTBI patients and CTE-NC in participating brain banks

描述参与脑库的 cTBI 患者和 CTE-NC 中导致 TReND 的病理的程度、分布和范围

• 批准号: 10483205
• 负责人: Douglas Hamilton Smith
• 金额: $ 16.29万
• 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/10483205
• 关键词: Age; Aging; Alzheimer' s disease pathology; Amyloid beta-Protein; Attention; Autopsy; Brain; Characteristics; Chronic; Clinical; Common Data Element; Communities; Complex; Consensus; Data; Diagnosis; Diagnostic; Elements; Evaluation; Exposure to; Individual; Injury; International; Lewy Bodies; Microscopy; Nerve Degeneration; Neurodegenerative Disorders; Output; Pathology; Patients; Pattern; Phase; Population; Prevalence; Protocols documentation; Reporting; Research Design; Research Project Grants; Risk; Sampling; Series; Severities; Stains; Standardization; Survivors; TBI Patients; Traumatic Brain Injury; aged; axonal degeneration; chronic traumatic encephalopathy; comparative; cost; digital; mild traumatic brain injury; neuroinflammation; neuron loss; neuropathology; protein TDP-43; tau Proteins; tau-1; tissue resource; validation studies; white matter

Research Project 1 SUMMARY There is growing concern over the association between traumatic brain injury (TBI) and progressive neurodegenerative changes, in particular those that are characterized as chronic traumatic encephalopathy (CTE). First recognized in boxers, it was not until descriptions of CTE pathology in non-boxer athletes attracted widespread attention. However, reflecting the paucity of cases described, current consensus criteria for the neuropathological assessment of CTE remain preliminary, with the associated clinical consequences of this pathology unclear. Furthermore, the narrow focus on CTE and its characteristic tau pathologies has come at the cost of characterizing many other neuropathologies that have also been observed in CTE cases and in all forms of TBI. Current reporting in CTE largely focuses on p-tau pathologies, which are thought to define its pathognomonic neuropathology. However, rather than a single proteinopathy, wider, unbiased autopsy reporting of TBI related neurodegeneration (TReND) in chronic TBI (cTBI) survivors across a full spectrum of injury severities documents far more varied complex neuropathologies. Furthermore, the pathologies encountered in cTBI patients often are mixed, with multiple proteinopathies, particularly in aged patients. As such, there is growing recognition that TReND in TBI survivors is a complex polypathology, just one element of which might be described by current definitions of CTE. We propose to characterize the extent, distribution and range of pathologies contributing to TReND in cTBI patients across a spectrum TBI types and severities. In addition, we will develop and validate operational criteria for the neuropathological diagnosis of TReND pathologies using established protocols that have proven successful for wider neurodegenerative disease.

研究项目1 总结 越来越多的人关注创伤性脑损伤（TBI）和进行性脑损伤之间的关系。 神经退行性变化，特别是以慢性创伤性脑病为特征的变化 （CTE）。首先在拳击手中认识到，直到非拳击手运动员的CTE病理学描述吸引了 引起广泛关注。然而，反映了所描述的病例的缺乏， CTE的神经病理学评估仍然是初步的，与此相关的临床后果 病理学不清楚。此外，对CTE及其特征性tau病理学的狭隘关注已经达到了 在CTE病例中观察到的许多其他神经病理特征的成本， TBI的形式。目前CTE的报道主要集中在p-tau病理学，其被认为定义了其在CTE中的作用。 特异性神经病理学然而，与单一的蛋白质病相比， 慢性TBI（cTBI）幸存者中TBI相关神经变性（TReND）的全方位损伤 severities记录了更复杂的神经病理学。此外， cTBI患者通常是混合的，具有多种蛋白质病，特别是在老年患者中。因此， 越来越多的人认识到TBI幸存者的TReND是一种复杂的多病理学，其中一个因素可能 根据当前CTE的定义进行描述。我们建议描述的程度，分布和范围 在一系列TBI类型和严重程度中，导致cTBI患者TReND的病理学。另外我们 将开发和验证TReND病理学神经病理学诊断的操作标准， 已建立的方案已被证明对更广泛的神经退行性疾病是成功的。