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.

项目概要/摘要 重复性脑震荡和亚脑震荡脑外伤，如接触运动和军事中所经历的那样 从长远来看，部署与破坏性神经退行性疾病有关，例如慢性 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 很大程度上难以捉摸。众所周知，TBI 可通过轴突急剧诱导 β 淀粉样蛋白增加。 损害，有证据表明这可以演变成淀粉样斑块，但其程度、持续时间和 这种增加的影响尚未在活人中得到充分研究，特别是在轻度 TBI 中，这是 最常见的形式。诱导的有毒淀粉样蛋白种类的后果令人担忧，尤其是 考虑到最近的证据表明 β 淀粉样蛋白可能通过 肾上腺素能系统，说明了淀粉样蛋白可能导致神经毒性的新途径，即使它 升高是适度的，随后通过正常的生理过程或药理学清除 干预措施。虽然这对 AD 研究具有巨大影响，但它也提出了诱人的可能性 淀粉样蛋白是 TBI 后神经变性风险的一个重要因素，可能包括最轻微的神经变性 年轻运动员和军人经常接触到的形式。幸运的是，有强大且 测量活体大脑中β淀粉样蛋白的灵敏方法。在目标 1 中，我们将采用最经过验证的、 定量 PET/MR 成像技术（具有动脉输入功能和房室建模的 11C-PiB） 敏感地测量大学接触运动运动员在赛季前后的大脑淀粉样蛋白水平。 我们的主要假设是，季节过后，全球皮质淀粉样蛋白分布量将会更高。在 目标 2，我们将探讨该测量与创伤性轴索损伤的相关测量的关系 相关白质（使用 DTI MRI 的分数各向异性，与 PET 同时采集）、血浆 生物标志物和加速计测量的客观暴露变量。虽然这是一个初步的 机制研究，它可能会为整个领域的诊断和预防方法带来重要的新方向 全方位的 TBI 严重程度。