Exploring preclinical amyloid pathology with optical microscopy

用光学显微镜探索临床前淀粉样蛋白病理学

• 批准号: 10193586
• 负责人: Mohammad Abbas Yaseen
• 金额: $ 32.75万
• 依托单位: NORTHEASTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-15 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10193586
• 关键词: Exploring; preclinical; amyloid; pathology; optical

ABSTRACT This project will investigate early pathophysiological hallmarks of Alzheimer's disease (AD) using newly- developed microscopy tools. Alzheimer's disease (AD) is a devastating, irreversible neurodegenerative disorder that currently has no effective treatment. Long before the first clinically-observable cognitive and behavioral symptoms of Alzheimer's disease (AD) arise, a “preclinical” incubation phase transpires, lasting up to ~2 decades and involving a myriad of changes at the cellular and vascular level. More detailed knowledge of these intricate, multifaceted preclinical alterations and their contributions to subsequent cognitive deterioration is essential to fill critical gaps in our understanding of AD's pathogenesis and to comprehensively assess the therapeutic potential of candidate treatments. Exploring the neurovascular and metabolic alterations that occur during the preclinical phase of AD could hold the key to understanding how to detect and counteract AD- related neurodegeneration. We have developed an array of innovative optical microscopy tools to noninvasively characterize multiple facets of cerebral blood flow and energy metabolism in living animal brains. These advanced techniques are ideally suited to characterize the convoluted progression of multiple pathophysiological features of preclinical AD. Specifically, these investigations will explore on a microscopic scale how accumulation of amyloid β and neuroinflammation, notable AD pathophysiological hallmarks, affect the neurovascular unit, cerebral oxygenation, energy metabolism, and cerebral blood flow. The results will help us understand in greater detail the multifactorial structural and functional changes that happen in the brain and collectively give rise to clinically-observable cognitive deficiencies. This project will yield insight into the mechanisms underlying AD pathogenesis with unprecedented detail, and it will facilitate the development of new therapeutic techniques widely applicable to the growing population of at-risk aging citizens.

抽象的 该项目将使用新的 - 开发的显微镜工具。阿尔茨海默氏病（AD）是一种毁灭性的，不可逆的神经退行性 目前没有有效治疗的疾病。早在第一个临床观察到的认知和 阿尔茨海默氏病（AD）的行为症状是一种“临床前”孵化相，持续 到约20年，涉及细胞和血管水平的无数变化。更详细的了解 这些复杂的，多方面的临床前改变及其对随后的认知确定的贡献 对于填补我们对AD发病机理的理解并全面评估的关键空白至关重要 候选治疗的治疗潜力。探索发生的神经血管和代谢改变 在AD的临床前阶段，可以持有了解如何检测和抵消AD的关键 相关的神经变性。我们已经开发了一系列创新的光学显微镜工具 无创的表征活动物大脑中脑血流和能量代谢的多个方面。 这些高级技术非常适合表征多重的复杂进展 临床前AD的病理生理特征。具体而言，这些调查将在微观上进行探索 扩展淀粉样β和神经炎症的积累如何影响AD病理生理标志， 结果将有助于神经血管单元，脑充氧，能量代谢和脑血流量。 我们更详细地了解大脑中发生的多因素结构和功能变化 共同引起临床观察的认知缺陷。 该项目将以前所未有的细节和 它将促进新的治疗技术的发展，广泛适用于不断增长的人群 处于危险的衰老公民。