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.

摘要 该项目将研究阿尔茨海默病（AD）的早期病理生理学特征，使用新的- 开发了显微镜工具。阿尔茨海默病（AD）是一种破坏性的、不可逆的神经退行性疾病， 目前尚无有效治疗方法的疾病。早在第一个临床上可观察到的认知和 阿尔茨海默病（AD）的行为症状出现，一个“临床前”潜伏期发生，持续到 到约20年，涉及细胞和血管水平的无数变化。更详细的知识 这些复杂的、多方面的临床前改变及其对随后认知恶化的贡献 对于填补我们对AD发病机制的理解中的关键空白以及全面评估 候选治疗的治疗潜力。探索神经血管和代谢的变化， 在AD的临床前阶段，可以掌握了解如何检测和对抗AD的关键- 相关的神经变性我们开发了一系列创新的光学显微镜工具， 非侵入性地表征活体动物大脑中脑血流和能量代谢的多个方面。 这些先进的技术非常适合于表征多个复杂的进展， 临床前AD的病理生理学特征。具体来说，这些研究将在微观上探索 衡量淀粉样蛋白β的积累和神经炎症，显着的AD病理生理学标志，如何影响 神经血管单位、脑氧合、能量代谢和脑血流。这些结果将帮助 我们更详细地了解了大脑中发生的多因素结构和功能变化， 共同引起临床上可观察到的认知缺陷。 该项目将以前所未有的细节深入了解AD发病机制， 它将促进新的治疗技术的发展，广泛适用于不断增长的人口， 处于危险中的老年人