Sleep, brain cleaning and Alzheimer’s

June 25, 2014

Sleep, brain cleaning and Alzheimer’s

According to recent research at the Neuromedicine Center of the University of Rochester directed by Maiken Nedergaard, recently published in “Science” magazine, an important function of sleep is to perform vast cleaning through its own lymphatic system, independent from the body which is separated from the brain through the blood brain barrier. It is a system that controls the flow of cerebrospinal fluid through the action of the glial cells: for this reason, the system has been dubbed “glymphatic.” The energy consumption of this system is such that it is able to feed itself in the waking state. It is understandable that the timely removal of waste in the brain is essential. Thanks to new, sophisticated imaging technologies, such as two-photon microscopy, the researchers were able to observe the motions of the cerebrospinal fluid in vivo, confirming that the glymphatic system is almost ten times more active during sleep and that while one is sleeping a quantity of beta protein ammiloide is removed significantly higher than when one is awake. Another surprising discovery made in the course of the research is that during sleep the flow of cerebrospinal fluid in the interstitial spaces of the brain increases by 60 percent, as if its cells somehow “shrink” to allow for a more effective cleaning of the brain tissue.
Recent experiments on mice have shown that with sleep deprivation the typical plaques of Alzheimer’s disease appear earlier and more extensively Washington University School of Medicine in St. Louis (in Science Express, the online version of Science magazine).
The report sleep/wake cycle, according to studies by Jae-Eun Kang, regulates the levels of amyloid beta protein: it increases at night and decreases during the day. According to results, sleep deprivation is able to determine an increase of the beta amyloid protein by 25 percent.
Another study by Randall Bateman of Barnes-Jewish Hospital has instead measured the levels of amyloid beta protein in the cerebrospinal fluid of humans, in fact finding that they were generally higher during waking and lowest during sleep.

Recent studies have correlated orexin, a protein directly involved in the regulation of sleep, with the amyloid plaques characteristic of Alzheimer’s. Orexin is a neuropeptide with many functions. On one hand it plays a very important role in appetite control interacting with leptin and with the endocannabinoid system, while on the other hand it is implicated in the mechanisms of regulation of the sleep/wake cycle to the point to be involved in the increase in amyloid plaques typical in Alzheimer’s disease.
According to David M. Holtzman, director of the Department of Neurology, School of Medicine, Barnes-Jewish Hospital, Orexin or compounds with which it interacts may become new targets for the treatment of Alzheimer’s.