Good sleep is a means of preventing Alzheimer's disease
According to the results of a new study, insomnia, the habit of going to bed late and an irregular night's sleep may be associated with the development of Alzheimer's disease.
According to one of the authors of the work, David Holtzman, a neurologist from the University of Washington, the results obtained are preliminary evidence that sleep disorders in middle age increase the risk of developing Alzheimer's disease in old age. Scientists have found that the concentration of beta-amyloid, a peptide whose accumulation is associated with the development of Alzheimer's disease, increases significantly during periods of chronic sleep deprivation.
The mechanisms of Alzheimer's disease are triggered when beta-amyloid is transformed from a soluble monomeric form into oligomers, protofibrils and fibrils, which form plaques in the intercellular fluid of the brain that damage neurons. Jae-Eun Kang from Washington University (St. Louis) and her colleagues were studying the physiological factors controlling this process when they came across the relationship between sleep and Alzheimer's disease. The group has developed a new technique, beta–amyloid microdialysis, which allows hourly monitoring of changes in the level of this protein in animal and human brain tissues. When testing the new system, they noticed that the level of beta-amyloid in both mice and humans increases significantly during the daytime and decreases at night.
After it became clear that these variations were not associated with periods of darkness or light, the authors studied the effect of different sleep patterns on the level of beta-amyloid. An increase in the waking period of mice by 6 hours per day caused a sharp increase in the level of beta-amyloid, which indicates a relationship between the duration of waking time and the level of beta-amyloid. The accumulation of beta-amyloid plaques in the brains of mice with chronic lack of sleep – the animals were allowed to sleep only 4 hours a day for 21 days – significantly exceeded this indicator in mice of the same age with a normal sleep/wakefulness regime.
On slices of the cerebral cortex (D, E) and hippocampus
– a structure that plays a key role in the processes of memorization (E, F) –
impressive difference between the number of amyloid plaques in the control group of mice
and in animals exhausted by lack of sleep.
The range of fluctuations in the level of beta-amyloid turned out to be very significant – during the day its concentration can vary by 25-40%. Surprised by this fact, the researchers devoted their further work to studying the molecular mechanisms underlying such radical changes associated with sleep duration.
The administration of orexin (orexin) to animals, a neuropeptide hormone that controls the state of wakefulness, significantly increased the level of beta-amyloid. Subsequent blocking of orexin by its receptor antagonist almorexant, currently being studied by pharmaceutical companies as a candidate for an insomnia remedy, reduced the concentration of beta-amyloid and eliminated its daily fluctuations.
The results obtained by the authors demonstrate for the first time that environmental conditions and behavior can directly affect the metabolism of beta-amyloid and the development of Alzheimer's disease. This fact indicates that the level of beta-amyloid can be adjusted directly by therapeutic methods.
The authors demonstrated that daily administration of almorexant for 8 weeks significantly suppresses the formation of amyloid plaques in the brain of mice. However, they emphasize that in order to recognize the compound as suitable for therapeutic use, it is necessary to devote more than one year to research work.
In the near future, they plan to work with epidemiologists to analyze the relationship between sleep disorders and Alzheimer's disease, as well as to continue studying the mechanism regulated by orexin.
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of The Scientist: Late nights linked to Alzheimer's.
02.10.2009