Prevention of Alzheimer's disease: inactivate orexin and sleep longer

Wakefulness Protein May be a Target for Alzheimer's disease prevention

NanoNewsNet based on WU St. Louis: Protein that rouses the brain from sleep may be target for Alzheimer's preventionA protein that stimulates the brain to wake up from sleep may be a target for the prevention of Alzheimer's disease.

These are the conclusions from a study by scientists from the Washington University School of Medicine in St. Louis (Washington University School of Medicine in St. Louis).

In the last few years, researchers have established a link between sleep disorders and Alzheimer's disease. So, they proved, in humans and mice, that sleep loss contributes to the formation of plaques in the brain, characteristic of Alzheimer's disease, and also increases the risk of dementia.

A new study shows that removing the orexin protein makes mice sleep longer and significantly slows down the formation of plaques in the brain.

"This suggests that we should pay attention to orexin as a potential target for the prevention of Alzheimer's disease," says study leader David Holtzman, MD, head of the Department of Neurology. "Blocking orexin in order to increase the duration of sleep in patients with its abnormalities or, perhaps, even improve the quality of sleep in healthy people may be a way to reduce the risk of developing Alzheimer's disease. This deserves further study."

Brain plaques, consisting mainly of a protein called beta-amyloid, accumulate in the brain before the onset of symptoms of Alzheimer's disease, such as memory loss, personality change and disorientation. The formation of these plaques continues during the progression of the disease. Scientists believe that slowing down or stopping their accumulation can slow down or even stop the disease.

In this study, Dr. Holtzman and his colleagues worked with genetically modified mice whose brains accumulated amyloid, which is characteristic of Alzheimer's disease. The offspring of these mice, obtained from crossing with mice deprived of the orexin gene, slept longer, and two times fewer plaques formed in the brain of animals compared to mice with a normal amount of orexin.

Orexin is produced in the cells of the hypothalamus that maintain a state of wakefulness. "These cells have appendages that carry orexin throughout the brain, and the protein acts as a switch," explains Professor Holtzman. "If you stimulate the synthesis of orexin in sleeping mice, they immediately wake up."

Low levels of orexin are associated with narcolepsy, a disease characterized by a violation of sleep-wake cycles. During the 12-hour period when orexin-producing mice are more active, mice without orexin usually sleep an extra hour or more.

With an artificial increase in orexin levels throughout the brain, the mice stayed awake longer, and more plaques formed in their brains. But the change in the level of orexin only in a part of the brain, which did not affect the duration of sleep, had no effect on the formation of plaques.

"The fact that orexin affects the formation of plaques only when it also affects sleep suggests the need to think carefully about how to make it a target for the prevention of Alzheimer's disease," Professor Holtzman comments on the results of the experiments. "But the degree of reduction in plaque formation that we observed in mice is so high that studying the potential of orexin is still of great interest."

Currently, he and his colleagues are studying the effect of sleeping pills on the production of beta-amyloid and plaque accumulation. The FDA recently approved the drug Belsomra, the first highly selective orexin receptor antagonist, and scientists hope to evaluate its effect on the risk of developing Alzheimer's disease.

Article by Roh et al. Potential role of orexin and sleep modulation in the pathogenesis of Alzheimer’s disease
published in The Journal of Experimental Medicine.

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