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

慢性创伤性脑病：检测、诊断、病程和危险因素

• 批准号: 10314027
• 负责人: JEFFREY L. CUMMINGS
• 金额: $ 235.39万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-12-15 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10314027
• 关键词: Address; Age; Alzheimer' s Disease; Amygdaloid structure; Amyloid; Astrocytes; Attention; Award; Behavior; Behavioral; Biological Markers; Boxing; Brain; Brain Chemistry; Brain Concussion; Brain Diseases; Case Study; Clinical; Cognitive; Consensus; Consensus Workshop; Control Groups; Corpus Callosum; Country; Data; Databases; Degenerative Disorder; Dementia; Deposition; Detection; Diagnosis; Diagnostic; Diffusion Magnetic Resonance Imaging; Disease; Epilepsy; Exposure to; Frequencies; Functional Magnetic Resonance Imaging; Genetic; Genetic Polymorphism; Gold; Grant; Growth; Head; Image; Impairment; Individual; Intervention; Life; Liquid substance; Literature; Longitudinal Studies; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Manufactured football; Measures; Methods; Modeling; Moods; Motor; Multicenter Studies; Nerve Degeneration; Neurocognitive; Neurodegenerative Disorders; Neurologic; Neurons; Pattern; Plasma; Play; Positron-Emission Tomography; Prevention; Process; Proxy; Publishing; Recording of previous events; Reporting; Research Personnel; Rest; Risk; Risk Factors; Science; Septum Pellucidum; Signs and Symptoms; Sports; Subgroup; Symptoms; Syndrome; Tauopathies; Testing; Thinness; Tracer; Trauma; Traumatic Brain Injury; Validation; Validity and Reliability; Variant; Writing; Youth; brain abnormalities; chronic traumatic encephalopathy; clinical diagnosis; clinical diagnostics; college; contact sports; data portal; design; diagnostic accuracy; diagnostic criteria; effective intervention; experience; follow-up; head impact; high risk; high school; in vivo; infancy; insight; men; military service; multidisciplinary; neuroimaging; neuropathology; novel; physical abuse; preventive intervention; public health relevance; service member; subconcussion; symposium; tau Proteins; tau-1; tool; uptake; white matter

 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.

 描述（由申请人提供）：慢性创伤性脑病（CTE）是一种神经退行性疾病，其特征在于tau蛋白异常形式的独特沉积，其模式与其他疾病（包括阿尔茨海默病（AD））不同。CTE最常见于职业接触性运动员（例如，拳击、足球），这些人头部受到反复打击，导致脑震荡和亚脑震荡创伤。神经病理学证实的CTE已经在17岁的个体和仅在高中或大学参加运动的运动员中报道。它也被发现在非运动员谁经历了重复的头部撞击，包括癫痫患者，身体虐待的受害者，和军人。与媒体对CTE的广泛关注所推断的相反，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疾病。尽管CTE的神经病理学特征近年来已变得进一步明确，但CTE的临床表现仍没有得到很好的表征，尽管自20世纪初以来在拳击手中已有“拳击员痴呆”的病例报告。临床诊断标准最近才被 出版，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，迫切需要开发用于在生命期间检测和诊断CTE的准确方法，以便可以开发用于预防和治疗的有效干预措施。此外，尽管重复头部撞击的历史是CTE的必要风险因素，但仅凭它是不够的。有必要了解头部撞击暴露的哪些具体方面使个体患CTE的风险增加，并检查该风险的潜在遗传修饰剂。为了满足这些需求，我们提出了一个多学科，多中心，对高暴露于重复头部撞击的前运动员的纵向研究（120名有或无症状的前NFL球员）或中度暴露于重复性头部撞击（60名有和无症状的前大学足球运动员）和60名无症状的对照组，年龄男性，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液体生物标志物，用于检测生活中的CTE，包括使用一种新的PET示踪剂来测量异常脑tau蛋白的量;（2）表征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）调查CTE的遗传和头部撞击暴露危险因素;（6）与国内外研究人员分享项目数据，以加快我们对这种疾病的认识和治疗。

项目成果

Amyloid PET across the cognitive spectrum in former professional and college American football players: findings from the DIAGNOSE CTE Research Project.

• DOI: 10.1186/s13195-023-01315-5
• 发表时间: 2023-10-05
• 期刊: Alzheimer's research & therapy

Exposure to Repetitive Head Impacts Is Associated With Corpus Callosum Microstructure and Plasma Total Tau in Former Professional American Football Players.

• DOI: 10.1002/jmri.27774
• 发表时间: 2021-12
• 期刊: Journal of magnetic resonance imaging : JMRI
• 作者: Kochsiek J;O'Donnell LJ;Zhang F;Bonke EM;Sollmann N;Tripodis Y;Wiegand TLT;Kaufmann D;Umminger L;Di Biase MA;Kaufmann E;Schultz V;Alosco ML;Martin BM;Lin AP;Coleman MJ;Rathi Y;Pasternak O;Bouix S;Stern RA;Shenton ME;Koerte IK
• 通讯作者: Koerte IK

Proteomic Profiling of Extracellular Vesicles Separated from Plasma of Former National Football League Players at Risk for Chronic Traumatic Encephalopathy.

• DOI: 10.14336/ad.2020.0908
• 发表时间: 2021-09
• 期刊: Aging and disease
• 影响因子: 7.4
• 作者: Muraoka S;DeLeo AM;Yang Z;Tatebe H;Yukawa-Takamatsu K;Ikezu S;Tokuda T;Issadore D;Stern RA;Ikezu T
• 通讯作者: Ikezu T

Endophenotype-based in silico network medicine discovery combined with insurance record data mining identifies sildenafil as a candidate drug for Alzheimer's disease.

• DOI: 10.1038/s43587-021-00138-z
• 发表时间: 2021-12
• 期刊: NATURE AGING
• 作者: Fang, Jiansong;Zhang, Pengyue;Zhou, Yadi;Chiang, Chien-Wei;Tan, Juan;Hou, Yuan;Stauffer, Shaun;Li, Lang;Pieper, Andrew A.;Cummings, Jeffrey;Cheng, Feixiong
• 通讯作者: Cheng, Feixiong

Sex differences in white matter alterations following repetitive subconcussive head impacts in collegiate ice hockey players.

• DOI: 10.1016/j.nicl.2017.11.020
• 发表时间: 2018
• 期刊: NeuroImage. Clinical
• 作者: Sollmann N;Echlin PS;Schultz V;Viher PV;Lyall AE;Tripodis Y;Kaufmann D;Hartl E;Kinzel P;Forwell LA;Johnson AM;Skopelja EN;Lepage C;Bouix S;Pasternak O;Lin AP;Shenton ME;Koerte IK
• 通讯作者: Koerte IK