Clinical and Molecular Biology of Acute and Chronic Traumatic Encephalopathies

描述（由申请人提供）：本提案要求支持由Sam Gandy、Steven T.德科斯基和安麦基，这将是在基斯通，科罗拉多从2012年2月26日至3月2日。急性创伤性脑损伤（TBI）及其长期神经退行性并发症（统称为慢性创伤性脑病，或CTE）越来越多地被认为是主要的公共卫生问题，特别是在运动相关的头部损伤和战场爆炸（军事）暴露的背景下。随着神经学、精神病学和神经变性现象与职业运动员以及从伊拉克和阿富汗战场返回的退伍军人有关，人们对这些问题的认识有所提高。在这次为期3天的会议的最初几次会议上，将审查头部受伤的物理学以及与运动有关和与爆炸有关的综合征的流行病学和神经精神方面。在功能性神经影像学和在脑脊液和血浆中的肽和蛋白质的快速和方便的测定的进展将审查其可能的病理生物学意义，以及它们的身份作为可能的生物标志物。以后的会议将集中在CTE和主要的神经退行性疾病，如阿尔茨海默病（AD），额颞叶痴呆症和肌萎缩侧索硬化症之间的重叠。CTE与聚集的蛋白质或蛋白质片段的积累有关，包括tau、TDP-43、阿尔茨海默氏淀粉样前体蛋白（APP）和APP代谢物淀粉样蛋白-β。新的实验疗法研究针对这些异常蛋白质结构在损伤严重程度和后续结果中的作用。目前在AD临床试验中的降低A β的药物改善了啮齿动物模型中急性脑创伤后的结果，表明了潜在的治疗干预途径。由于载脂蛋白E（APOE）同种型是急性重度和轻度重复性TBI结果的重要决定因素，因此本次会议在时间和地点上与ApoE，阿尔茨海默病和脂蛋白生物学的Keystone研讨会会议相吻合。开幕式全体会议和可选的第四天会议可供那些有兴趣了解更多有关APOE的基础生物学和/或临床干预措施的人使用。 公共卫生相关性：公众对创伤性脑损伤（TBI）病理后果的认识已经提高：1）车辆碰撞的流行和开发和完善乘客安全功能的努力; 2）认识到与高接触运动相关的重复性轻度TBI的潜在临床意义（最初是拳击，最近是美式足球）;（3）现代战争，特别是冲击伤，TBI被认为是一种“标志性损伤”，目前影响着超过一半的爆炸暴露幸存者。关于急性和慢性创伤性脑病的临床和分子生物学的Keystone研讨会会议将审查和严格检查运动和军事TBI的流行病学，分子方面和临床谱，及其长期神经退行性并发症。

DESCRIPTION (provided by applicant): This proposal requests support for a Keystone Symposia meeting entitled Clinical and Molecular Biology of Acute and Chronic Traumatic Encephalopathies, organized by Sam Gandy, Steven T. DeKosky and Ann McKee, which will be held in Keystone, Colorado from February 26 - March 2, 2012. Acute traumatic brain injury (TBI) and its long-term neurodegenerative complications (known collectively as chronic traumatic encephalopathy, or CTE) are recognized increasingly as major public health issues, especially in the context of sports-related head injury and battlefield blast (military) exposure. Awareness of these issues has risen as neurological, psychiatric, and neurodegenerative phenomena are associated with professional athletes and with veterans returning from Iraqi and Afghan theaters. The physics of head injury, as well as the epidemiological and neuropsychiatric aspects of sports-related and blast-related syndromes, will be reviewed in the initial sessions of this 3-day meeting. Advances in functional neuroimaging and in the rapid and convenient determination of peptides and proteins in the cerebrospinal fluid and plasma will be reviewed in terms of their possible pathobiological significance as well as their identities as possible biomarkers. Later sessions will focus on the overlap between CTE and major neurodegenerative diseases, such as Alzheimer's disease (AD), frontotemporal dementia, and amyotrophic lateral sclerosis. CTE is associated with accumulation of aggregated proteins or protein fragments, including tau, TDP-43, the Alzheimer's amyloid precursor protein (APP), and the APP metabolite, amyloid-beta. New experimental therapeutics research targets the roles these abnormal protein structures play in injury severity and subsequent outcome. Abeta- lowering medications, currently in clinical trials for AD, improve outcome following acute brain trauma in rodent models, suggesting a pathway toward potential therapeutic interventions. Because apolipoprotein E (APOE) isotype is an important determinant of outcome from acute severe as well as mild repetitive TBI, this meeting coincides in time and venue with the Keystone Symposia meeting on ApoE, Alzheimer's and Lipoprotein Biology. Opening plenary sessions and an optional fourth day of sessions are available for those interested in learning more about basic biology and/or clinical interventions related to APOE. PUBLIC HEALTH RELEVANCE: Public awareness of the pathological consequences of traumatic brain injury (TBI) has been elevated by: 1) the prevalence of vehicular crashes and efforts to develop and perfect passenger safety features; 2) recognition of the potential clinical significance of repetitive mild TBI associated with high-contact sports (initially boxing, and more recently, American football); and 3) modern warfare, especially blast injuries, with recognition of TBI as a "signature injury" currently affecting over half of those who survive blast exposure. The Keystone Symposia meeting on Clinical and Molecular Biology of Acute and Chronic Traumatic Encephalopathies will review and critically examine the epidemiology, molecular aspects and clinical spectrum of sports and military TBI, and its long-term neurodegenerative complications.