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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.

项目总结: