Chronic Traumatic Encephalopathy: Detection, Diagnosis, Course, and Risk Factors

 描述(申请人提供)：慢性创伤性脑病(CTE)是一种神经退行性疾病，其特征是异常形式的tau蛋白以一种不同于包括阿尔茨海默病(AD)在内的其他疾病的独特模式沉积。CTE最常见于职业接触性运动运动员(如拳击、足球)，他们的头部受到反复打击，导致脑震荡和亚震荡创伤。神经病理学证实的CTE已经在17岁的个体和只参加过高中或大学体育运动的运动员中得到了报道。在反复头部撞击的非运动员中也发现了这种情况，包括癫痫患者、身体虐待的受害者和服兵役人员。与媒体对CTE的广泛关注所推断的相反，CTE的科学仍处于初级阶段；关键问题仍然存在，如它是否是一种常见疾病。尽管近年来CTE的神经病理特征得到了进一步的阐明，但尽管自1900年初S以来的拳击性痴呆症文献中已有病例报道，但CTE的临床表现仍不够典型。临床诊断标准直到最近才被提出 已发表，缺乏有效性。为诊断其他神经退行性疾病而开发的神经成像和液体生物标记物仅用于初步研究。因此，迫切需要开发准确的方法来检测和诊断生活中的CTE，以便能够开发有效的预防和治疗干预措施。此外，尽管反复头部撞击史是CTE的必要危险因素，但仅有这一点是不够的。有必要了解头部撞击暴露的哪些具体方面使个人患CTE的风险增加，并检查这种风险的潜在遗传修饰因素。为了解决这些需求，我们建议对高度暴露于重复头部撞击的前运动员(120名有和没有症状的前NFL球员)或中等暴露于重复头部撞击的前NFL球员(60名有症状和没有症状的前大学橄榄球运动员)进行一项多学科、多中心的纵向研究，并将60名没有任何重复头部撞击暴露或创伤性脑损伤病史的无症状的同龄男性作为对照组。我们建议的目的是：(1)收集和分析用于检测生活中CTE的神经影像和液体生物标志物，包括使用一种新的PET示踪剂来测量异常脑tau的数量；(2)表征CTE的临床表现；(3)研究CTE在三年时间内的进展；(4)完善和验证临床诊断标准；(5)调查CTE的遗传和头部撞击暴露的危险因素；以及(6)与国内外研究人员共享项目数据，以加快我们对这种疾病的了解和治疗。

 DESCRIPTION (provided by applicant): Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease characterized by a distinct deposition of an abnormal form of the tau protein in a pattern that is unique from other diseases, including Alzheimer's disease (AD). CTE has been found most often in professional contact sport athletes (e.g., boxing, football) who have been subjected to repetitive blows to the head resulting in concussive and subconcussive trauma. Neuropathologically-confirmed CTE has been reported in individuals as young as 17 and in athletes who only played sports through high school or college. It also has been found in non-athletes who experienced repetitive head impacts, including epileptics, victims of physical abuse, and military service members. In contrast to what may be inferred by the extensive media attention on CTE, the science of CTE remains in its infancy; critical questions remain, such as whether or not it is a common disease. Although the neuropathological features of CTE have become further clarified in recent years, the clinical presentation of CTE is still not well characterized, even though there have been case reports in the literature of "dementia pugilistica" in boxers since the early 1900's. Clinical diagnostic criteria have only recently been published and lack validation. Neuroimaging and fluid biomarkers developed for the diagnosis of other neurodegenerative diseases have only been used in preliminary studies. There is thus an urgent need to develop accurate methods for detecting and diagnosing CTE during life so that effective interventions for prevention and treatment can be developed. Moreover, though a history of repetitive head impacts is a necessary risk factor for CTE, it alone is not sufficient. There is a need to understand what specific aspects of the head impact exposure places an individual at increased risk for CTE and to examine potential genetic modifiers of that risk. To address these needs, we propose a multidisciplinary, multicenter, longitudinal study of former athletes with high exposure to repetitive head impacts (120 former NFL players with and without symptoms) or medium exposure to repetitive head impact (60 former college football players with and without symptoms) and a control group of 60 asymptomatic same-age men without any history of repetitive head impact exposure or traumatic brain injury. The aims of our proposal are: (1) to collect and analyze neuroimaging and fluid biomarkers for the detection of CTE during life, including the use of a novel PET tracer to measure the amount of abnormal brain tau; (2) to characterize the clinical presentation of CTE; (3) to examine the progression of CTE over a three year period; (4) to refine and validate diagnostic criteria for the clinical diagnosisof CTE; (5) to investigate genetic and head impact exposure risk factors for CTE; and (6) to share project data with researchers across the country and abroad in order to expedite growth in our understanding and treatment of this disease.