Researchers have shown that chronic sleep deprivation in a mouse model of Alzheimer's disease makes Alzheimer's brain plaques appear earlier and more often. Orexin, a protein that helps regulate the sleep cycle, appears to be directly involved in the increase.

The findings of this study are some of the first indications that sleep loss could play a role in the genesis of neurodegenerative disorders like Alzheimer's disease

Not only does the risk of Alzheimer's disease increase with age, the sleep/wake cycle also starts to break down, with older adults progressively getting less and less sleep.

A technique called in vivo microdialysis was used 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 Alzheimer's 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.

Electroencephalography (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. Blocking a hormone previously linked to stress and amyloid beta production had no effect on these changes, suggesting that they weren't caused by the stress of sleep deprivation. Three weeks of chronic sleep deprivation accelerated amyloid plaque deposition in the brain.

When researchers injected orexin into the brains of the mice, mice stayed awake longer, and amyloid beta levels increased. When they blocked both orexin receptors, amyloid beta levels were significantly lower and animals were awake less.

The researchers are considering epidemiological studies of whether chronic sleep loss in young and middle-aged adults increases risk of Alzheimer's disease later in life.

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References:
1. Kang J-E, Lim MM, Bateman RJ, Lee JJ, Smyth LP, Cirrito JR, Fujiki N, Nishino S, Holtzman DM. Amyloid beta dynamics are regulated by orexin and the sleep-wake cycle. Science Express, Sept. 24, 2009.

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