CTE and Posttraumatic Neurodegeneration: Neuropathology and Ex Vivo Imaging

CTE 和创伤后神经变性：神经病理学和离体成像

• 批准号: 9315530
• 负责人: Ann C. McKee
• 金额: $ 6.92万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9315530
• 关键词: Age; Alzheimer' s Disease; American; Amygdaloid structure; Amyotrophic Lateral Sclerosis; Asses; Athletic; Autopsy; Autoradiography; Behavior; Behavioral; Binding; Biological Markers; Blast Injuries; Blinded; Brain; Brain Concussion; Brain Stem; Brain region; Characteristics; Clinical; Clinical Data; Collaborations; Common Data Element; Comorbidity; Consensus; Corpus Callosum; DNA-Binding Proteins; Data; Data Storage and Retrieval; Databases; Dementia; Deposition; Development; Diagnosis; Diagnostic; Diffusion Magnetic Resonance Imaging; Disease; Ensure; Foundations; Freezing; Frontotemporal Lobar Degenerations; Functional Magnetic Resonance Imaging; Gold; Health; Hippocampus (Brain); Histologic; Hotlines; Hypothalamic structure; Image; Imaging Device; Immunohistochemistry; Impaired cognition; Impairment; Incidence; Incubated; Individual; Late Effects; Lewy Body Disease; Life; Ligand Binding; Ligands; Medical Examiners; Medical Records; Memory Loss; Mental Depression; Military Personnel; Moods; Nerve Degeneration; Nervous System Trauma; Neurites; Neurodegenerative Disorders; Pathologist; Pathology; Patients; Positron-Emission Tomography; Prevalence; Procedures; Protocols documentation; Public Health; Qualifying; Recording of previous events; Registries; Research; Research Infrastructure; Research Personnel; Resolution; Resources; Risk Factors; Sampling; Scanning; Scheme; Secure; Severities; Slice; Slide; Specimen; Staging; Staining method; Stains; Statistical Methods; Substance abuse problem; Symptoms; Tauopathies; Techniques; Temporal Lobe; Testing; Thalamic structure; Thick; Tissues; Traumatic Brain Injury; United States National Institutes of Health; Work; alpha synuclein; axon injury; biobank; chronic traumatic encephalopathy; cognitive change; cognitive function; data sharing; density; diagnosis standard; disturbance in affect; executive function; experience; frontal lobe; gray matter; high risk; imaging biomarker; in vivo; loss of function; mild traumatic brain injury; neuroimaging; neuropathology; outreach program; programs; prospective; protein aggregate; repository; tau Proteins; tau mutation; tool; web based interface; white matter

DESCRIPTION (provided by applicant): Traumatic brain injury (TBI) is associated clinically with progressive cognitive decline and dementia and pathologically with axonal injury and the deposition of multiple aggregated proteins. Repetitive mild TBI can trigger chronic traumatic encephalopathy (CTE), a unique tauopathy, and single TBI can provoke an Alzheimer's-like neurodegeneration. Unfortunately, the only way to diagnose these posttraumatic neurodegenerations, including CTE, is by post-mortem brain examination. In order to conduct prospective research into the incidence, prevalence, risk factors, clinical course, and ultimately, treatment for posttraumatic neurodegeneration, consensus criteria for diagnosis as well as objective biomarkers for disease must first be established. This initiative will assemble a multicenter team of expert neuroscientists to evaluate the late effects of TBI, including single and repetitive TBI of varying severity, and CTE, using histological examination of postmortem bio specimens and neuroimaging tools as a foundation to develop in vivo diagnostics. As a first aim, this proposal will bring together a team of 5 accomplished neuropathologists in neurodegenerative disease to establish consensus criteria for the post-mortem diagnosis of CTE. This team will also define the stages of CTE pathology, the features that differentiate CTE from other neurodegenerations and the effects of substance abuse, and the characteristics of posttraumatic neurodegeneration after single TBI. As a second aim, this proposal will establish a national bio specimen and data bank for TBI (Understanding Neurological Injury and Traumatic Encephalopathy (UNITE) bio bank) by developing a nationwide brain donor registry and hotline to acquire high quality bio specimens and data. The UNITE bank will use strictly standardized protocols and a web-based interface to ensure that tissue and data are readily available to qualified investigators. Comprehensive retrospective clinical data including clinical symptoms, brain trauma and substance abuse history, and medical records (including common data elements) will be entered into a secure database. Behavioral/ mood dysfunction, cognitive changes, substance abuse and traumatic exposure will be correlated with quantitative assessment of the multifocal tauopathy, Ass deposition and axonal injury. As a third aim, neuroimaging signatures of the neuropathology will be determined in post-mortem tissue using high spatial resolution diffusion tensor imaging (DTI) and autoradiography using a highly selective PET ligand for tau. Quantitative assessment of axonal injury, tau, and Ass will be correlated with ex vivo DTI abnormalities and tau ligand autoradiography. Pilot neuroimaging studies of individuals at high risk for the development of CTE will also be conducted in the final 2 years of the proposal. This proposal will determine the clinical and neuroimaging correlates of CTE and posttraumatic neurodegeneration and create the groundwork for establishing their incidence and prevalence. This study will have a tremendous impact on public health of millions of Americans and greatly increase our understanding of the latent effects of brain trauma.

描述（由申请人提供）：创伤性脑损伤（TBI）在临床上与进行性认知能力下降和痴呆症有关，并在病理上与轴突损伤以及多种聚集的蛋白质的沉积有关。重复的轻度TBI可以触发慢性创伤性脑病（CTE），一种独特的tauopathy，单个TBI会引起阿尔茨海默氏症的类神经变性。不幸的是，诊断包括CTE在内的创伤后神经退行性的唯一方法是通过验尸后的脑检查。为了对发病率，患病率，危险因素，临床过程以及最终的前瞻性研究 需要首先建立创伤后神经退行性的治疗，诊断的共识标准以及客观的生物标志物。该倡议将组装一个由专家神经科学家组成的多中心团队，以评估TBI的后期影响，包括不同严重程度的单一和重复性TBI，以及CTE，使用对事后生物标本的组织学检查和神经成像工具作为在VIVO诊断中发展的基础。作为第一个目的，该提案将在神经退行性疾病中组成一支由5名成熟的神经病理学家组成的团队，以建立CTE后验尸诊断的共识标准。该团队还将定义CTE病理学的阶段，将CTE与其他神经退行性变化和药物滥用的影响以及单个TBI后创伤后神经变性的特征进行了特征。作为第二个目的，该提案将通过开发全国性的脑捐赠注册表和热线，以获取高质量的生物标本和数据来建立国家生物标本和数据库（了解神经系统损伤和创伤性脑病（UNITE）生物银行）。 Unite Bank将使用严格的标准化协议和基于Web的界面，以确保合格的研究人员很容易获得组织和数据。全面的回顾性临床数据，包括临床症状，脑外伤和药物滥用病史以及病历（包括常见数据元素），将输入安全数据库。行为/情绪功能障碍，认知变化，药物滥用和创伤性暴露将与对多焦点扭曲，屁股沉积和轴突损伤的定量评估有关。作为第三目的，使用高空间分辨率扩散张量成像（DTI）和放下自显影，将在验尸组织中确定神经病理学的神经影像学特征，并使用TAU的高选择性PET配体。轴突损伤，TAU和ASS的定量评估将与离体DTI异常和Tau配体放射自显影相关。在提案的最后两年中，还将进行对CTE发展高风险的个体的试验神经影像学研究。该建议将确定CTE和创伤后神经变性的临床和神经成像相关性，并为确定其发病率和流行率创造了基础。这项研究将对数百万美国人的公共卫生产生巨大影响，并大大增加我们对脑创伤潜在影响的理解。

项目成果

Correspondence of mean apparent propagator MRI metrics with phosphorylated tau and astrogliosis in chronic traumatic encephalopathy.

慢性创伤性脑病中平均表观传播 MRI 指标与磷酸化 tau 蛋白和星形胶质细胞增生的对应关系。

• DOI: 10.1093/braincomms/fcad253
• 发表时间: 2023
• 期刊: Brain communications
• 影响因子: 4.8
• 作者: Gangolli,Mihika;Pajevic,Sinisa;Kim,JoongHee;Hutchinson,ElizabethB;Benjamini,Dan;Basser,PeterJ
• 通讯作者: Basser,PeterJ

A review of neuroimaging findings in repetitive brain trauma.

• DOI: 10.1111/bpa.12249
• 发表时间: 2015-05
• 期刊: Brain pathology (Zurich, Switzerland)
• 作者: Koerte IK;Lin AP;Willems A;Muehlmann M;Hufschmidt J;Coleman MJ;Green I;Liao H;Tate DF;Wilde EA;Pasternak O;Bouix S;Rathi Y;Bigler ED;Stern RA;Shenton ME
• 通讯作者: Shenton ME