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

基本信息

批准号：
10241895
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
项目类别：
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/10241895
关键词：
Admixture Aging Alzheimer&apos 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

Admixture Aging Alzheimer&apos 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

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项目摘要

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 概括越来越关注创伤性脑损伤（TBI）与进步性之间的关联神经退行性变化，尤其是被描述为慢性创伤性脑病（CTE）的变化。第一的在拳击手中认识到，直到后来报道了非拳击运动员类似病理的报道，长期才 TBI的后果引起了人们的关注。最近和初步共识标准提案CTE 作为一种独特的神经退行性病理学，尽管该病理的相关临床后果保持不清楚。重要的是，越来越多的共识是，整个合并症的流行率很高神经退行性疾病，包括AD，Lewy身体疾病和额颞Lobar变性。尽管，目前在CTE中报告的主要重点是提出的“病理学” tau病理学，这是异质性与TBI（CTBI）慢性存活相关的神经退行性疾病神经病理学不好描述。在这里，我们将评估神经病理学变化的范围，这些变化在TBI之间共享或唯一相关神经变性（趋势）与其他神经退行性疾病（包括阿尔茨海默氏病）（AD），Lewy身体疾病和额颞叶变性。具体而言，通过评估 275例病例的神经退行性疾病尸检队列，与CTBI队列研究IOD匹配研究项目 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。重要的是，通过检查进一步的450例案例，我们还将确定是否是否与其他神经退行性疾病过程一样，趋势病理学也可以在神经退行性中观察到没有TBI病史的疾病病例。