Disrupted sleep can accelerate the progression of Alzheimer’s disease, say scientists from the Washington University School of Medicine (WUSM). The scientists have identified a brain protein regulated by the natural sleep cycle, or circadian rhythm that accelerates the accumulation of toxic amyloid plaques associated with the inflammatory disease.

The brain protein in question is called YKL-40: high levels of it have been found in the cerebrospinal fluid of those suffering from the Alzheimer’s disease; these levels rise as the disease progresses.

“The gene for YKL-40 came up (during screening) as highly regulated by clock genes,” said Erik Musiek, WUSM associate professor of neurology. “That was really interesting because it is a well-known biomarker for Alzheimer’s.”

Further investigation into the correlation between YKL-40 and Alzheimer’s disease demonstrated that the circadian rhythm controls how much YKL-40 is produced.“If you have inflammation in the morning, you might get lots of YKL-40; if you get inflammation in the evening, when the clock’s in a different phase, you might get less YKL-40.”

The WUSM scientists also studied genetically modified mice lacking the gene for YKL-40 and found that these mice featured more microglia as they aged – microglia are protective immune cells that surround and prevent amyloid plaques from spreading.

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“This YKL-40 protein probably serves as a modulator of the level of microglial activation in the brain,” Musiek added. “When you get rid of the protein, it appears the microglia are more activated to eat up the amyloid. It’s a subtle thing, a tweak in the system, but it seems to be enough to substantially reduce the total amyloid burden.”

The scientists then examined this idea in human subjects, drawing on genetic data on 778 subjects from aging and dementia studies and finding only a quarter of them featured a genetic variant that lowers levels of YKL-40; cognitive function declined 16% more slowly in that group.

“If your circadian clock is not quite right for years and years – you routinely suffer from disrupted sleep at night and napping during the day – the cumulative effect of chronic dysregulation could influence inflammatory pathways such that you accumulate more amyloid plaques.

“We hope that a better understanding of how the circadian clock affects YKL-40 could lead to a new strategy for reducing amyloid buildup in the brain.”