Sleep Quality and Decreasing Amyloid-Beta Levels in the Human Brain

Brendan Lucey, MD
Washington University School of Medicine (Saint Louis, MO)
Year Awarded:
2016
Grant Duration:
July 1, 2016 to June 30, 2020
Disease:
Alzheimer's Disease
Award Amount:
$300,000
Grant Reference ID:
A2016180S
Award Type:
Standard
Award Region:
US Midwestern
Brendan Lucey, MD

Sleep Quality and Human Amyloid-Beta Kinetics

Summary

The deposition of amyloid-beta protein (Aβ) in the brain is a key first step in Alzheimer’s disease (AD). Recent work has shown that sleep decreases the concentration of Aβ in the brains of mice and humans. In mice, decreasing the amount of sleep reduced both the Aβ concentration and deposition in the brain, suggesting that sleep could be a therapy to prevent AD. Key questions remain, however, before AD prevention trials using sleep can begin in humans. This study proposes to answer several of these questions:  1) does poor sleep quality increase Aβ and 2) does improving sleep quality in poor sleepers decrease Aβ? 

Details

The deposition of amyloid-β (Aβ) in the brain is a key first step in Alzheimer’s disease (AD). Recent work has shown that sleep decreases the concentration of Aβ in the brains of mice and humans. In mice, decreasing the amount of sleep both reduced the Aβ concentration and deposition in the brain suggesting that sleep could be a therapy to prevent AD.

My study investigates whether poor sleep quality increases Aβ and if improving sleep quality decreases Aβ. We are able to measure differences in Aβ concentration, production, and clearance in the human central nervous system (CNS) using Aβ stable isotope labeling kinetics (Aβ SILK).  In Aim 1, individuals with poor sleep quality and individuals with good sleep quality, both treated with placebo, undergo Aβ SILK labeling to determine sleep-related differences in Aβ concentration and production.  In Aim 2, individuals with poor sleep quality, treated with either placebo or a drug approved as a treatment for insomnia, called suvorexant (Belsomra®), undergo Aβ SILK labeling.

Many recent studies have pointed to an association between sleep and AD, however there is no direct experimental evidence in humans of a sleep-related mechanism that could increase AD risk. My study will increase our understanding of how AD and sleep are related. For instance, individuals with poor sleep quality are predicted to have greater Aβ concentration and production compared to individuals with good sleep quality. Once complete, my study will answer key questions regarding the relationship between sleep and Aβ, as well as whether AD prevention trials using sleep are feasible.  Further, these studies may launch a novel field of research that identifies new targets for AD treatment.

About the Researcher

Brendan Lucey is an assistant professor of neurology at Washington University School of Medicine. He received his undergraduate degree from the University of Vermont and his medical degree from the Johns Hopkins University School of Medicine. After completing a neurology residency at Washington University and a clinical neurophysiology fellowship at Brigham and Women's Hospital, he served for four years on active duty in the United States Air Force. Dr. Lucey returned to Washington University in 2012, and pursued research into the relationships between sleep, aging, and Alzheimer's disease.

Personal Story

Recent work in mice showing a relationship between sleep and Aβ excited me with the possibility of using sleep to prevent or delay Alzheimer's disease (AD). My work has focused on translating these studies to humans, and I am very hopeful that sleep interventions will play a role in preventing AD. I am grateful for BrightFocus Foundation's support of my research project. Awards such as this one are critically important for early-stage investigators like myself, in order to develop exciting new areas of research.

Publications

 
 

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