A Connection Between Sleep and Alzheimer's?

You shouldn't stay up all night worrying about it, but a new study has found a connection between a lack of sleep and a biomolecule thought to be important in the development of Alzheimer's disease.

In both humans and mice, levels of a peptide called amyloid-β rise during waking hours and decline during sleep, researchers have found. They also report that sleep-deprived mice are more prone to developing deposits of amyloid-β, called plaques, like those found in the brains of Alzheimer's patients. Although far from proven, the finding suggests that sleep disorders could be a risk factor for Alzheimer's. On a brighter note, it also hints at new avenues of treatment.

Many lines of evidence suggest that the naturally occurring amyloid-β builds up in the brain over many years in people who develop Alzheimer's disease, beginning long before people show signs of memory loss. But very little is known about what factors might influence levels of the peptide in the brain, says David Holtzman, a neurologist at Washington University in St. Louis in Missouri.

To investigate, Holtzman and colleagues conducted a series of experiments with mice in which they inserted a tiny tube into the brain to collect samples of the fluid circulating in the space between cells. Sampling from the hippocampus, a crucial memory region that is one of the first to be ravaged by Alzheimer's disease, the researchers found that amyloid-β levels peaked when the animals were awake and fell off during sleep. They found a similar pattern in 10 healthy people who consented to spinal taps to allow researchers to sample their cerebrospinal fluid.

The researchers also probed the effects of chronic sleep deprivation on mice that are genetically prone to developing amyloid plaques. To keep the mice awake, the researchers placed each on a small platform surrounded by water, which gave them no room to lie down and doze off. Mice who remained awake for 20 hours a day for 3 weeks developed more amyloid plaques than their well-rested peers, the researchers found. On the other hand, a drug that blocks receptors for orexin, a hormone that promotes wakefulness, reduced plaque formation in the same strain of mice, the team reports online today in Science.

The findings suggest that people who are chronically sleep deprived may have higher levels of amyloid-β that make them more susceptible to Alzheimer's disease, Holtzman says. He says the team has been talking with researchers who do clinical sleep studies about combing their databases for any signs that people with a history of sleep disorders are more prone to Alzheimer's. "No one has ever studied that," he says. The team also wants to investigate using drugs that interfere with orexin to thwart Alzheimer's disease.

"I find it really cool that sleep is a modulator of amyloid-β production," says Sam Sisodia, a molecular neurobiologist at the University of Chicago in Illinois. That fits with other evidence that amyloid-β rises and falls with levels of synaptic activity, Sisodia says. But any breakthrough treatments for Alzheimer's are a long way off, he cautions. "It's another insight, another glimmer of hope."