Sleep Quality and Human Amlyoid-Beta Kinetics

睡眠质量和人类β淀粉样蛋白动力学

基本信息

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
项目类别：
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&apos s Disease Alzheimer&apos 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

项目摘要

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.

项目摘要：医学博士Brendan Lucey博士是一位积极进取的身体科学家，对睡眠，衰老和神经退行性疾病，例如阿尔茨海默氏病。他最近被提升为助理教授华盛顿大学的神经病学（任期），现在正在寻求支持他的进一步心态着重于阿尔茨海默氏病的新型治疗策略。在华盛顿开创性研究的基础上大学，卢西博士现在正在研究不同的睡眠状况如何（例如睡眠剥夺，诱导睡眠用药物治疗，正常的睡眠控制）会影响中枢神经系统（CNS）的产生，清除和淀粉样蛋白β（Aβ）的浓度。他发现睡眠剥夺显着增加了中枢神经系统Aβ和初步发现表明，睡眠效率较差的个体中CNSAβ的类似增加也会增加（即睡眠质量不佳）。使用稳定的同位素标记为氨基酸来确定体内Aβ的产生和清除率，Lucey博士将测试：1）如果CNSAβ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）如果对待个人用诱导睡眠药物治疗的睡眠效率不佳（suvorexant，双奥甲蛋白受体拮抗剂）将与对照组相比，CNSAβ产生，清除率和浓度降低。他的短期目标是通过建立学术来解决阿尔茨海默氏病的基本和有影响力的问题职业，通过独立资金（R01）扩大他的转化研究小组，并获得世界领先了解和治疗没有和治疗的老年人没有和治疗睡眠问题的专业知识神经退行性疾病，例如阿尔茨海默氏病。卢西博士的长期目标是发展一个令人兴奋的研究计划研究睡眠，衰老和阿尔茨海默氏病之间的相互关系。了解这些关系可能会推动新治疗的发展以防止或延迟阿尔茨海默氏病。为了实现这些目标，他招募了一位出色的经验调查员兰德尔·贝特曼（Randall Bateman）博士的老化研究以及职业发展咨询小组睡眠研究，老年医学和阿尔茨海默氏病领域的国际领导人（保罗·肖博士，大卫·霍尔茨曼（David Holtzman）和大卫·卡尔（David Carr））。他的职业发展计划包括：1）经常与他的导师和咨询小组； 2）聚焦于神经变性，衰老和睡眠的出席和表现半人物； 3）临床试验设计，数据管理，衰老和质谱的相关课程； 4）负责任的研究进行的持续培训。华盛顿大学医学院有杰出的Mentalship的杰出记录，尤其是K获奖者，并且有多个专注于衰老的实验室和神经退行性疾病。这将为心态提供丰富而支持的科学环境在衰老研究中。 Lucey博士有足够的（约400平方英尺）实验室空间和设备来实现这一目标研究项目。