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.

项目概要： Brendan Lucey 博士是一位积极进取的医学科学家，对睡眠、衰老和衰老等领域有着浓厚的兴趣。他最近晋升为助理教授。华盛顿大学神经病学博士（终身教授），现在正在寻求进一步的指导支持，因为他专注于阿尔茨海默病的新型治疗策略，以华盛顿的开创性研究为基础。大学的 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）如何影响睡眠质量。药物、正常睡眠控制）会影响中枢神经系统（CNS）的产生、清除和他发现睡眠不足会显着增加中枢神经系统 Aβ 的浓度。初步研究结果表明，睡眠效率差的个体中枢神经系统 Aβ 也会出现类似的增加（即睡眠质量差）。使用稳定同位素标记的氨基酸来确定体内 Aβ 的产生和清除率，Lucey 博士将测试：1) CNS Aβ 的产生、清除和浓度是否在 2) 与睡眠效率良好的个体相比，治疗睡眠效率较差的个体；睡眠效率差的人用睡眠诱导药物（suvorexant，一种双重食欲素受体拮抗剂）治疗会与对照相比，减少 CNS Aβ 的产生、清除和浓度。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和有影响力的问题职业生涯，通过独立资助（R01）扩大他的转化研究小组，并获得世界领先在理解和治疗老年人睡眠问题方面的专业知识 Lucey 博士的长期目标是开发一种令人兴奋的药物来治疗阿尔茨海默病等神经退行性疾病。研究项目调查睡眠、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开发，以预防或延迟为了实现这些目标，他招募了一位经验丰富的杰出研究人员来研究阿尔茨海默病。老龄化研究导师兰德尔·贝特曼 (Randall Bateman) 博士以及职业发展顾问小组睡眠研究、老年病学、衰老和阿尔茨海默氏病领域的国际领导者（Paul Shaw 博士、 David Holtzman 和 David Carr）。他的职业发展计划包括：1）与他的频繁会面。导师和顾问小组；2) 参加以神经退行性疾病、衰老和睡眠为主题的会议并发表演讲研讨会；3) 临床试验设计、数据管理、老化和质谱相关课程；华盛顿大学医学院有一个负责任的研究行为的持续培训。杰出的指导记录，特别是对 K 获奖者的指导，并拥有多个专注于老龄化的实验室这将为指导提供丰富且支持性的科学环境。 Lucey 博士拥有充足（约 400 平方英尺）的实验室空间和设备来完成这一任务。研究项目。