Sleep Quality and Human Amlyoid-Beta Kinetics

睡眠质量和人类β淀粉样蛋白动力学

• 批准号: 9927556
• 负责人: Brendan Patrick Lucey
• 金额: $ 15.57万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-15 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9927556
• 关键词: Abeta synthesis; Address; Adult; Affect; Aging; Alzheimer disease prevention; Alzheimer' s Disease; Alzheimer' s disease risk; American; Amino Acids; Amyloid; Amyloid beta-42; Amyloid beta-Protein; Beds; Brain; Catheters; Cell Death; Cerebrospinal Fluid; Clinical Trials Design; Cognitive; Control Groups; Data; Dementia; Development; Development Plans; Disease; Drug Controls; Elderly; Environment; Equipment; Foundations; Frequencies; Funding; Geriatrics; Goals; Hour; Human; Impaired cognition; Individual; Infusion procedures; Intercellular Fluid; International; Kinetics; Laboratories; Mass Spectrum Analysis; Measures; Mediating; Mentors; Mentorship; Metabolic Clearance Rate; Monitor; Mus; Nerve Degeneration; Neuraxis; Neurodegenerative Disorders; Neurofibrillary Tangles; Neurology; Participant; Pathogenesis; Pattern; Pharmaceutical Preparations; Pharmacology; Phase; Physicians; Placebos; Polysomnography; Prevalence; Prevention; Prevention trial; Production; Proteins; Public Health; Research; Research Personnel; Research Project Grants; Role; Sampling; Scientist; Senile Plaques; Sleep; Sleep Architecture; Sleep Deprivation; Sleep Disorders; Sleep disturbances; Stable Isotope Labeling; Testing; Time; Training; Translating; Translational Research; Universities; Wakefulness; Washington; Work; abeta deposition; actigraphy; aged; aging population; base; career; career development; data management; experience; extracellular; hypocretin; improved; in vivo; innovation; interest; medical schools; meetings; novel; novel therapeutics; prevent; professor; programs; receptor; response; responsible research conduct; sleep quality; sleep regulation; square foot; targeted treatment; tau aggregation; tenure track; treatment strategy

Project Summary: Dr. Brendan Lucey, MD is a highly-motivated physician-scientist with a strong interest in sleep, aging, and neurodegenerative disorders such as Alzheimer's disease. He was recently promoted to Assistant Professor of Neurology (tenure track) at Washington University and is now seeking support for further mentorship as he focuses on a novel treatment strategy for Alzheimer's disease. Building on pioneering research at Washington University, Dr. Lucey is now studying how different sleep conditions (e.g. sleep deprivation, sleep induction with medication, normal sleep control) affect the central nervous system (CNS) production, clearance, and concentration of amyloid-β (Aβ). He has found that sleep deprivation significantly increases CNS Aβ and preliminary findings suggest that a similar increase in CNS Aβ occurs in individuals with poor sleep efficiency (i.e. poor sleep quality). Using a stable isotope labeled amino acid to determine in vivo Aβ production and clearance rates, Dr. Lucey will test: 1) if CNS Aβ production, clearance, and concentration are increased in individuals with poor sleep efficiency compared to those with good sleep efficiency; 2) if treating individuals with poor sleep efficiency treated with a sleep-inducing drug (suvorexant, a dual orexin receptor antagonist) will decrease CNS Aβ production, clearance, and concentration compared to controls. His short-term goals are to address fundamental and impactful questions of Alzheimer's disease and sleep by establishing an academic career, expanding his translational research group with independent funding (R01), and gain world-leading expertise in the understanding and treatment of sleep problems in older adults without and with neurodegenerative disorders such as Alzheimer's disease. Dr. Lucey's long-term goal is to develop an exciting research program investigating the interrelationships between sleep, aging, and Alzheimer's disease. Understanding these relationships could drive the development of new treatments to prevent or delay Alzheimer's disease. To accomplish these goals, he has enlisted an outstanding experienced investigator in aging research as mentor, Dr. Randall Bateman, as well as a career development advisory panel of international leaders in the fields of sleep research, geriatrics, aging, and Alzheimer's disease (Drs. Paul Shaw, David Holtzman, and David Carr). His career development plan includes: 1) frequent meetings with his mentor and advisory panel; 2) attendance and presentation at neurodegeneration, aging, and sleep focused seminars; 3) relevant coursework in clinical trial design, data management, aging, and mass spectrometry; 4) on-going training in the responsible conduct of research. Washington University School of Medicine has an outstanding track record of mentorship, in particular with K awardees, and has multiple labs focused on aging and neurodegenerative disorders. This will provide a rich and supportive scientific environment for mentorship in aging research. Dr. Lucey has ample (~400 square feet) laboratory space and equipment to accomplish this research project.

项目概要： 博士Brendan Lucey医学博士是一位积极进取的医生科学家，对睡眠、衰老和 神经退行性疾病，如阿尔茨海默病。他最近被提升为助理教授 他是华盛顿大学神经病学教授（终身教职），现在正在寻求进一步指导的支持， 专注于阿尔茨海默病的新治疗策略。以华盛顿的开创性研究为基础 Lucey博士现在正在研究不同的睡眠条件（例如睡眠剥夺，睡眠诱导） 与药物，正常睡眠控制）影响中枢神经系统（CNS）的生产，清除， 淀粉样蛋白-β（Aβ）的浓度。他发现睡眠不足会显着增加中枢神经系统Aβ， 初步研究结果表明，睡眠效率差的个体也会出现类似的CNS Aβ增加 (i.e.睡眠质量差）。使用稳定同位素标记的氨基酸来测定体内Aβ的产生， 清除率，Lucey博士将测试：1）如果CNS Aβ的产生、清除和浓度增加， 与睡眠效率良好的人相比，睡眠效率差的人; 2）如果治疗个体 用睡眠诱导药物（suvorexant，一种双重食欲素受体拮抗剂）治疗睡眠效率差的患者， 与对照组相比，CNS Aβ产生、清除和浓度降低。他的短期目标是 通过建立学术机构来解决阿尔茨海默病和睡眠的基本且有影响力的问题 职业生涯，扩大他的翻译研究小组与独立的资金（R 01），并获得世界领先的 了解和治疗老年人睡眠问题的专业知识， 神经退行性疾病，如阿尔茨海默病。Lucey博士的长期目标是开发一种令人兴奋的 一项研究计划，调查睡眠、衰老和阿尔茨海默病之间的相互关系。 了解这些关系可以推动新疗法的发展，以防止或延迟 老年痴呆症为了实现这些目标，他招募了一位杰出的经验丰富的调查员， 作为导师，兰德尔贝特曼博士，以及一个职业发展咨询小组， 睡眠研究、老年医学、衰老和阿尔茨海默病领域的国际领导者（Drs. PaulShaw， 大卫霍尔茨曼和大卫卡尔）。他的职业发展计划包括：1）经常与他的 导师和咨询小组; 2）出席和介绍神经变性，老化，和睡眠集中 研讨会; 3）临床试验设计，数据管理，老化和质谱的相关课程; 4） 持续进行负责任的研究培训。华盛顿大学医学院有一个 杰出的指导记录，特别是与K获奖者，并有多个实验室专注于老龄化 和神经退行性疾病。这将为导师制提供丰富和支持性的科学环境 在衰老研究中。Lucey博士有充足的（约400平方英尺）实验室空间和设备来完成这项工作 研究项目。