The researchers also found that orexin, a protein that helps regulate the sleep cycle, appears to be directly involved in the increase. "Orexin or compounds it interacts with may become new drug targets for treatment of Alzheimer's disease," says senior author David M. Holtzman. "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.
The researchers 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 also showed that amyloid beta levels were generally higher when subjects were awake and lower when they slept.
To confirm the link, electroencephalography (EEG) was used on the mice. 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.
Depriving the mice of sleep caused a 25 percent increase in amyloid beta levels. Levels were lower when mice were allowed to sleep. 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, a 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.
MEDICA.de; Source: Washington University in St. Louis