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

研究项目1 摘要 人们越来越关注创伤性脑损伤 (TBI) 与进行性脑损伤之间的关联 神经退行性变化，特别是那些以慢性创伤性脑病为特征的变化 （热膨胀系数）。最初在拳击运动员中得到认可，直到非拳击运动员的 CTE 病理描述引起关注 广泛关注。然而，由于所描述的案例很少，目前的共识标准 CTE 的神经病理学评估仍处于初步阶段，其相关的临床后果 病理不清楚。此外，对 CTE 及其特征性 tau 病理学的狭隘关注已经出现 表征许多其他神经病理学的成本，这些神经病理学也在 CTE 病例和所有病例中观察到 TBI 的形式。目前 CTE 的报告主要集中在 p-tau 病理学上，这被认为定义了其 特征性神经病理学。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 TBI (cTBI) 幸存者在各种损伤中与 TBI 相关的神经变性 (TReND) 的关系 严重程度记录了更加多样化的复杂神经病理学。此外，遇到的病症 cTBI 患者通常是混合型，患有多种蛋白质病，尤其是老年患者。因此，有 人们越来越认识到 TBI 幸存者中的 TReND 是一种复杂的多病理学，仅其中一个因素就可能 由 CTE 的当前定义来描述。我们建议描述其范围、分布和范围 各种 TBI 类型和严重程度的 cTBI 患者中导致 TReND 的病理学。此外，我们 将开发和验证 TReND 病理神经病理学诊断的操作标准 已建立的协议已被证明对更广泛的神经退行性疾病是成功的。

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.