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 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，尤其是那些以慢性创伤性脑病为特征的改变 (CTE)。它最初在拳击手中被发现，直到关于非拳击手运动员CTE病理的描述才引起人们的注意。 受到广泛关注。然而，反映出所描述的案例很少，目前关于 CTE的神经病理学评估仍然是初步的，与此相关的临床后果。 病理不清楚。此外，对CTE及其特有的tau病理的狭隘关注已经出现。 在CTE病例和ALL中也观察到的许多其他神经病理特征的费用 TBI的形式。目前CTE的报道主要集中在p-tau病理上，这种病理被认为是定义其 病态神经病理学。然而，不是单一的蛋白质病，而是更广泛、公正的尸检报告 慢性颅脑损伤(CTBI)幸存者在各种损伤范围内与脑损伤相关的神经变性(趋势) 严重程度记录了更多样的复杂神经病理。此外，在中国遇到的病理情况 CTBI患者通常是混合型的，伴有多种蛋白病变，尤其是老年患者。因此，有 越来越多的人认识到，脑外伤幸存者的趋势是一个复杂的多病态，可能只是其中一个因素 由当前对CTE的定义来描述。我们建议表征的范围，分布和范围 不同类型和严重程度的cTBI患者的发病趋势与病理因素有关。此外，我们 将制定和验证用于趋势病理的神经病理诊断的操作标准 已建立的方案已被证明对更广泛的神经退行性疾病成功。