Late nights linked to Alzheimer's

Insomnia, late-night habits, and irregular sleep schedules may be linked to the onset of Alzheimer's disease, says a new linkurl:study;http://www.sciencemag.org/cgi/content/abstract/1180962 published online today in ScienceExpress. Image: FlickrCreativeCommons, CraigMDennis"Our results are preliminary evidence that sleep abnormalities midlife could put people at risk of Alzheimer's disease later,"

By | September 24, 2009

Insomnia, late-night habits, and irregular sleep schedules may be linked to the onset of Alzheimer's disease, says a new linkurl:study;http://www.sciencemag.org/cgi/content/abstract/1180962 published online today in ScienceExpress.
Image: FlickrCreativeCommons,
CraigMDennis
"Our results are preliminary evidence that sleep abnormalities midlife could put people at risk of Alzheimer's disease later," said linkurl:David Holtzman,;http://neuro.wustl.edu/aboutus/facultybiographies/holtzman.htm, a coauthor of the study and a neurologist at the Washington University School of Medicine. The group found that the concentration of amyloid-beta, a peptide whose build-up is linked to the onset of the disease, significantly increases during periods of sleep deprivation. Alzheimer's disease is triggered as amyloid-beta transforms from a soluble, monomeric form into oligomers, protofibrils, and fibrils that build up as plaque in the brain's interstitial fluid, damaging neurons. linkurl:Jae-Eun Kang;http://dbbs.wustl.edu/dbbs/website.nsf/AA/71C759F0CCA8FB4D86257613002461DA?OpenDocument at Washington University in St. Louis and her colleagues were studying the physiological factors regulating this process when they stumbled upon the connection between sleep and Alzheimer's disease. The team had just developed a new technology that allowed them to monitor peptides in animal and human brains on an hourly basis. As the researchers tried out their new system, called amyloid-beta microdialysis, they noticed peptide levels in both mice and men increased significantly during the day and dropped at night. After determining that light and dark exposure wasn't responsible for the variation, the researchers manipulated sleep behavior in mice to track the effects on the peptide. Mice were kept awake an additional six hours a day, during which amyloid-beta levels spiked, suggesting a link between the variations and wakefulness. Mice subjected to chronic sleep restriction - only allowed to sleep four hours a day for 21 days - had higher amyloid-beta plaque build-up in their brain than similar-aged mice with regular sleeping habits. "We were surprised that amyloid-beta levels were fluctuating by such wide margins -- 25, 30, even 40% -- over the course of the day," said Holtzman. "Once we knew the why, we wanted to know the how -- what molecular mechanism was causing such drastic variations corresponding with the sleep cycle." When Kang and her colleagues injected mice with orexin, a neuropeptide hormone that regulates wakefulness, amyloid-beta levels jumped significantly. The team then blocked orexin with a receptor antagonist called almorexant, which is currently being studied by pharmaceutical companies to treat insomnia, and found that it suppressed amyloid-beta levels and eliminated the natural diurnal fluctuations. "[The study] basically shows for the first time that environmental conditions and behavior can directly affect amyloid-beta metabolism and disease onset," linkurl:Christian Haas,;http://www.cipsm.de/en/aboutCIPSM/members/haassChristian/index.html?style=0, a biochemist at the Adolf Butenandt Institute in Munich, Germany, who was not involved in the study, said in an email. It suggests that "amyloid-beta metabolism should be directly targeted in therapeutic approaches." Kang and her colleagues found that doses of almorexant once daily for eight weeks reduced amyloid-beta plaque build up in mice. Holtzman warned, however, that years of further study are needed for researchers to determine whether the compound has potential as a therapy. He said the researchers now plan to work with epidemiologists to connect sleep disorders and Alzheimer's disease through case studies. The team also wants to continue researching the orexin pathway. "There are two receptors, OX1 and OX2, that bind orexin," said Holtzman. "In this study, we used a dual antagonist to block both, but we would really like to find out which of these is actually modifying the molecule" and affecting amyloid-beta concentrations.
**__Related stories:__***linkurl:Alzheimer's clue found;http://www.the-scientist.com/blog/display/55868/
[29th July 2009]*linkurl:Alzheimer's Pathology, circa 1906;http://www.the-scientist.com/article/display/55477/
[1st March 2009]*linkurl:Imaging early Alzheimer disease;http://www.the-scientist.com/article/display/13338/
[28th October 2002]

Comments

Avatar of: anonymous poster

anonymous poster

Posts: 5

September 24, 2009

A follow-up study would be valuable, to find out at what age the sleep deprivation makes a difference in amyloid-beta levels, and whether or not the change is easily reversed.\nThank you for reporting this finding.
Avatar of: Ada Criscione

Ada Criscione

Posts: 1

September 25, 2009

Interesting - now I would ask that question. Since the U.S. population is known world-wide for not getting enough sleep, due to stress, work schedules, insomnia, sleep-disorders, etc. where does it leave us as a nation? So the old saying, "Early to bed and early to rise makes a man (or woman) healthy, wealthy and wise" is not so far fetched after all.
Avatar of: Roberta Friedman

Roberta Friedman

Posts: 4

September 25, 2009

Many degenerative conditions of the brain are being linked to sleep deprivation so I am wondering who is going to show whether insomnia is merely an early warning sign that the brain is becoming damaged?
Avatar of: Louisa Tabatabai

Louisa Tabatabai

Posts: 3

September 25, 2009

I agree with Friedman's and Criscione's comments. \n
Avatar of: Jeremy Wickins

Jeremy Wickins

Posts: 9

September 25, 2009

As I seem to keep writing here, I look forward to reading more about this! \n\nSomething that occurs to me is, if this correlation is indeed a connection, what are the implications for people who work shifts?
Avatar of: Phil Ticehurst

Phil Ticehurst

Posts: 7

September 30, 2009

I agree with Roberta Friedman that the observed "correlation" between insomnia and brain damage does not prove that one caused the other or that one is a symptom of the other. However, the sleep deprivation study done with mice showed a dramatic effect (much bigger than one would expect from such a short study) of sleep deprivation and undesirable changes in brain chemistry. This is exciting data and I look forward to seeing the results of longer term tests such as finding which receptor is the active one (or both or something else). Great work!
Avatar of: Dov Henis

Dov Henis

Posts: 97

October 1, 2009

Two postings elsewhere, in addition to quite a few relevant postings in \nthe-scientist.com/community: \n\n"Sleep, Health And Immunity"\nhttp://www.sciencenews.org/index/generic/activity/view/id/43455/title/Narcolepsy_linked_to_immune_system\n\n"Life Is Simpler Than They Tell Us"\nhttp://www.articlesbase.com/science-articles/life-is-simpler-than-they-tell-us-817144.html\n\n\nDov Henis\n(Comments From The 22nd Century)

July 6, 2010

I've been noticing a pattern among people destined to have Alzheimers: They are insomniacs. This has led me to wonder whether lesions in the brain may effect the sleep center and then, with too little sleep, the brain suffers for lack of "re-charging". \n\nAs I started researching the concept, I came across this article in "The Scientist". I'm grateful for the research being done and hope the scientists will be looking at the idea that Alzheimers Disease may be the precipitator as well as the result of sleeplessness. \n\n

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