Sleep Quality and Human Amyloid-Beta Kinetics

Principal Investigator

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? 

Detailed Non-Technical Summary

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.

Publications

Lucey BP, Hicks TJ, McLeland JS, Toedebusch CD, Boyd J, Elbert DL, Patterson BW, Baty J, Morris JC, Ovod V, Mawuenyega KG, Bateman RJ. Effect of sleep on overnight cerebrospinal fluid amyloid β kinetics. Ann Neurol. 2018 Jan;83(1):197-204. doi: 10.1002/ana.25117. PMID: 29220873; PMCID: PMC5876097.

First published on: July 20, 2016

Last modified on: August 09, 2022