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

慢性创伤性脑病（CTE）是一种神经退行性疾病， 一种异常形式的tau蛋白的模式是独特的其他疾病，包括阿尔茨海默氏症， 疾病（AD）。CTE最常见于职业接触性运动员（例如，拳击，足球）谁 头部受到反复打击，造成震荡和亚震荡性创伤。 据报道，神经病理学证实的CTE发生在年仅17岁的个体和仅 在高中或大学里都是运动员它也被发现在非运动员谁经历了重复 头部撞击，包括癫痫患者、身体虐待的受害者和军人。与之相对的是 可以从媒体对CTE的广泛关注推断，CTE的科学仍然处于起步阶段;关键 问题仍然存在，例如它是否是一种常见病。虽然神经病理学特征的 近年来，CTE的发病率逐渐增高，但其临床表现仍不清楚 特征，即使在文献中有拳击手“拳击员痴呆”的病例报告， 从20世纪初开始临床诊断标准最近才发表，缺乏验证。 用于诊断其他神经退行性疾病的神经影像学和液体生物标志物仅 用于初步研究。因此，迫切需要开发用于检测和 在生活中诊断CTE，以便制定有效的预防和治疗干预措施。 此外，尽管重复头部撞击的历史是CTE的必要风险因素，但它本身并不是 足够了。有必要了解头部撞击暴露的哪些具体方面， 并检查该风险潜在遗传修饰剂。解决这些 需要，我们提出了一个多学科，多中心，纵向研究的前运动员高暴露于 重复性头部撞击（120名前NFL球员有和没有症状）或中度暴露于重复性 头部撞击（60名前大学足球运动员，有或没有症状）和对照组60名 无症状同龄男性，无任何重复头部撞击暴露或创伤性脑损伤史。 我们的建议的目的是：（1）收集和分析神经影像学和流体生物标志物，用于检测 生活中的CTE，包括使用新型PET示踪剂测量异常脑tau的量;（2） 描述CTE的临床表现;（3）检查CTE在三年内的进展; (4)完善和验证CTE的临床诊断标准;（5）研究CTE的遗传和头部疾病， CTE的影响暴露风险因素;（6）与全国各地的研究人员共享项目数据， 为了加快我们对这种疾病的理解和治疗的增长。

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 diagnosis of 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.