Does Contact Sport Induce Fibrillar Amyloid Deposition in the Brain?

接触性运动会引起大脑中纤维状淀粉样蛋白沉积吗？

• 批准号: 10302426
• 负责人: PAUL VASKA
• 金额: $ 42.73万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-22 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10302426
• 关键词: Accelerometer; Acute; Adrenergic Agents; Alleles; Alzheimer' s Disease; Amyloid; Amyloid beta-Protein; Amyloid deposition; Anisotropy; Biological Markers; Blood; Blood flow; Brain; Brain Concussion; Brain imaging; Craniocerebral Trauma; Deposition; Detection; Diagnosis; Diagnostic; Exhibits; Exposure to; Functional disorder; Future; Human; Imaging Techniques; Injury; Intervention; Lead; Link; Magnetic Resonance Imaging; Measures; Military Personnel; Modeling; Molecular; Nerve Degeneration; Neurodegenerative Disorders; Neurologic Dysfunctions; Neurological outcome; Pathway interactions; Pharmacology; Physiological; Physiological Processes; Plasma; Play; Population; Positron-Emission Tomography; Probability; Production; Proteins; Research; Research Design; Risk; Role; Seasons; Senile Plaques; Severities; Structure; System; Time; Traumatic Brain Injury; amyloid pathology; apolipoprotein E-4; axon injury; base; chronic neurologic disease; chronic traumatic encephalopathy; college; concussive symptom; contact sports; experience; fascinate; gray matter; head impact; hemodynamics; individual variation; longitudinal design; mild traumatic brain injury; molecular pathology; neurotoxicity; prevent; radiotracer; response; service member; subconcussion; tau Proteins; white matter

PROJECT SUMMARY/ABSTRACT Repetitive concussive and subconcussive brain trauma, as experienced in contact sports and military deployment, has been linked to devastating neurodegenerative disease in the long term, such as chronic traumatic encephalopathy (CTE) and Alzheimers disease (AD), but the mechanisms linking them remain largely elusive. It is well known that TBI can acutely induce increases in beta amyloid protein via axonal damage and there is evidence that this can evolve into amyloid plaques, but the magnitude, duration and implications of this increase have not been well studied in living humans, especially in mild TBI which is the most common form. The consequences of induced toxic amyloid species are worrisome, especially considering recent evidence that beta amyloid might directly stimulate production of tau protein via the adrenergic system, illustrating a new pathway through which amyloid may result in neurotoxicity even if its elevation is modest and subsequently cleared by normal physiological processes or pharmacological interventions. While this has enormous implications for AD research, it also raises the tantalizing possibility that amyloid is an important factor in the risk of neurodegeneration following TBI, perhaps including the mildest forms to which young athletes and service members are frequently exposed. Fortunately, there are robust and sensitive ways to measure beta amyloid in the living brain. In Aim 1, we will employ the most validated, quantitative PET/MR imaging techniques (11C-PiB with arterial input function and compartmental modeling) to sensitively measure brain levels of amyloid in college contact-sport athletes before and after a season of play. Our primary hypothesis is that global cortical amyloid distribution volume will be higher after the season. In Aim 2, we will explore relationships of this measure with related measures of traumatic axonal injury of associated white matter (using fractional anisotropy with DTI MRI, acquired simultaneously to PET), plasma biomarkers, and objective exposure variables measured by accelerometer. Although this is a preliminary mechanistic study, it could lead to vital new directions for diagnostic and preventative approaches across the full spectrum of TBI severity.

项目总结/摘要 重复性脑震荡和亚脑震荡性脑创伤，如在接触性运动和军事中所经历的 部署，已被链接到毁灭性的神经退行性疾病，在长期内，如慢性 创伤性脑病（CTE）和阿尔茨海默病（AD），但它们之间的联系机制仍然存在 很难捉摸众所周知，TBI可以通过轴突损伤急性诱导β淀粉样蛋白的增加， 有证据表明，这可以演变成淀粉样斑块，但幅度，持续时间和 这种增加的影响尚未在活体人类中得到很好的研究，特别是在轻度TBI中， 最常见的形式。诱导毒性淀粉样物质的后果令人担忧，特别是 考虑到最近的证据表明，β淀粉样蛋白可能直接刺激产生tau蛋白，通过 肾上腺素能系统，说明了一个新的途径，通过它淀粉样蛋白可能导致神经毒性，即使其 升高是适度的，随后通过正常的生理过程或药理学过程清除。 干预措施。虽然这对AD研究有着巨大的意义，但它也提出了一种诱人的可能性， 淀粉样蛋白是TBI后神经变性风险的重要因素，可能包括最轻微的神经变性。 年轻运动员和军人经常接触的形式。幸运的是， 测量活体大脑中β淀粉样蛋白的灵敏方法。在目标1中，我们将采用最有效的， 定量PET/MR成像技术（具有动脉输入功能和房室模型的11 C-PiB）， 灵敏地测量大学接触性运动员在一个赛季比赛前后的大脑淀粉样蛋白水平。 我们的主要假设是，全球皮质淀粉样蛋白分布量将在赛季结束后更高。在 目的2：探讨该指标与创伤性轴索损伤相关指标的关系， 相关白色物质（使用DTI MRI的分数各向异性，与PET同时采集），血浆 生物标志物和通过加速计测量的客观暴露变量。虽然这是初步的 机械研究，它可能会导致整个诊断和预防方法的重要新方向， 全面的创伤性脑损伤严重程度