Featured Research

from universities, journals, and other organizations

Sleep Loss Linked To Increase In Alzheimer's Plaques

Date:
September 25, 2009
Source:
Washington University School of Medicine
Summary:
Chronic sleep deprivation in a mouse model of Alzheimer's disease makes Alzheimer's brain plaques appear earlier and more often, researchers report. They also found that orexin, a protein that helps regulate the sleep cycle, appears to be directly involved in the increase.

Chronic sleep deprivation in a mouse model of Alzheimer's disease makes Alzheimer's brain plaques appear earlier and more often, researchers at Washington University School of Medicine in St. Louis report online this week in Science Express.

Related Articles


They also found that orexin, a protein that helps regulate the sleep cycle, appears to be directly involved in the increase.

Neurodegenerative disorders like Alzheimer's disease and Parkinson's disease often disrupt sleep. The new findings are some of the first indications that sleep loss could play a role in the genesis of such disorders.

"Orexin or compounds it interacts with may become new drug targets for treatment of Alzheimer's disease," says senior author David M. Holtzman, M.D., the Andrew and Gretchen Jones Professor and chair of the Department of Neurology at the School of Medicine and neurologist-in-chief at Barnes-Jewish Hospital. "The results also suggest that we may need to prioritize treating sleep disorders not only for their many acute effects but also for potential long-term impacts on brain health."

Holtzman's laboratory uses a technique called in vivo microdialysis to monitor levels of amyloid beta in the brains of mice genetically engineered as a model of Alzheimer's disease. Amyloid beta is a protein fragment that is the principal component of Alzheimer's plaques.

Jae-Eun Kang, Ph.D., a post-doctoral fellow in Holtzman's lab, noticed that brain amyloid beta levels in mice rose and fell in association with sleep and wakefulness, increasing in the night, when mice are mostly awake, and decreasing during the day, when they are mostly asleep.

A separate study of amyloid beta levels in human cerebrospinal fluid led by Randall Bateman, M.D., assistant professor of neurology and a neurologist at Barnes-Jewish Hospital, also showed that amyloid beta levels were generally higher when subjects were awake and lower when they slept.

To confirm the link, Kang learned to use electroencephalography (EEG) on the mice at the Sleep and Circadian Neurobiology Laboratory at Stanford University with researchers Seiji Nishino, M.D., Ph.D., and Nobuhiro Fujiki, M.D., Ph.D. The EEG readings let researchers more definitively determine when mice were asleep or awake and validated the connection: Mice that stayed awake longer had higher amyloid beta levels.

"This makes sense in light of an earlier study in our lab where John Cirrito, Ph.D., showed that increases in synaptic activity resulted in increased levels of amyloid beta," Holtzman notes. "The brain's synapses may generally be more active when we're awake."

Depriving the mice of sleep caused a 25 percent increase in amyloid beta levels. Levels were lower when mice were allowed to sleep. Blocking a hormone previously linked to stress and amyloid beta production had no effect on these changes, suggesting that they weren't caused by the stress of sleep deprivation, according to Holtzman.

Researchers elsewhere had linked mutations in orexin to narcolepsy, a disorder that is characterized by excessive daytime sleepiness. The brain has two kinds of receptors for orexin, which is also associated with regulation of feeding behavior.

When Holtzman's group injected orexin into the brains of the mice, mice stayed awake longer, and amyloid beta levels increased. When researchers used a drug called almorexant to block both orexin receptors, amyloid beta levels were significantly lower and animals were awake less.

Miranda M. Lim, M.D., Ph.D., a neurology resident and post-doctoral researcher in Holtzman's lab, performed long-term behavioral experiments with the mice. She found that three weeks of chronic sleep deprivation accelerated amyloid plaque deposition in the brain. In contrast, when mice were given almorexant for two months, plaque deposition significantly decreased, dropping by more than 80 percent in some brain regions.

"This suggests the possibility that a treatment like this could be tested to see if it could delay the onset of Alzheimer's disease," says Holtzman.

Holtzman notes that not only does the risk of Alzheimer's increase with age, the sleep/wake cycle also starts to break down, with older adults progressively getting less and less sleep. Investigators are considering epidemiological studies of whether chronic sleep loss in young and middle-aged adults increases risk of Alzheimer's disease later in life.

Holtzman also plans to learn more of the molecular details of how orexin affects amyloid beta.

"We would like to know if there are ways to alter orexin signaling and its effects on amyloid beta without necessarily modifying sleep," he says.

Additional studies will address the questions of whether increased amyloid beta during wakefulness is connected to increased synaptic activity and whether some aspect of sleep lowers amyloid beta levels independent of synaptic activity.


Story Source:

The above story is based on materials provided by Washington University School of Medicine. The original article was written by Michael Purdy. Note: Materials may be edited for content and length.


Journal Reference:

  1. Kang J-E, Lim MM, Bateman RJ, Lee JJ, Smyth LP, Cirrito JR, Fujiki N, Nishino S, Holtzman DM. Amyloid beta dynamics are regulated by orexin and the sleep-wake cycle. Science, Sept. 24, 2009

Cite This Page:

Washington University School of Medicine. "Sleep Loss Linked To Increase In Alzheimer's Plaques." ScienceDaily. ScienceDaily, 25 September 2009. <www.sciencedaily.com/releases/2009/09/090924141742.htm>.
Washington University School of Medicine. (2009, September 25). Sleep Loss Linked To Increase In Alzheimer's Plaques. ScienceDaily. Retrieved November 25, 2014 from www.sciencedaily.com/releases/2009/09/090924141742.htm
Washington University School of Medicine. "Sleep Loss Linked To Increase In Alzheimer's Plaques." ScienceDaily. www.sciencedaily.com/releases/2009/09/090924141742.htm (accessed November 25, 2014).

Share This


More From ScienceDaily



More Mind & Brain News

Tuesday, November 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Are Female Bosses More Likely To Be Depressed?

Are Female Bosses More Likely To Be Depressed?

Newsy (Nov. 24, 2014) — A new study links greater authority with increased depressive symptoms among women in the workplace. Video provided by Newsy
Powered by NewsLook.com
Winter Can Cause Depression — Here's How To Combat It

Winter Can Cause Depression — Here's How To Combat It

Newsy (Nov. 23, 2014) — Millions of American suffer from seasonal depression every year. It can lead to adverse health effects, but there are ways to ease symptoms. Video provided by Newsy
Powered by NewsLook.com
Could Your Genes Be The Reason You're Single?

Could Your Genes Be The Reason You're Single?

Newsy (Nov. 21, 2014) — Researchers in Beijing discovered a gene called 5-HTA1, and carriers are reportedly 20 percent more likely to be single. Video provided by Newsy
Powered by NewsLook.com
Milestone Birthdays Can Bring Existential Crisis, Study Says

Milestone Birthdays Can Bring Existential Crisis, Study Says

Newsy (Nov. 21, 2014) — Researchers find that as people approach new decades in their lives they make bigger life decisions. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins