Your body clock linked to Alzheimer’s disease risk, study finds

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In a recent study at Washington University School of Medicine in St. Louis, researchers found that the brain protein YKL-40 may play a big role in the link between Alzheimer’s and sleep dysfunction.

They found that YKL-40 is both regulated by body clock genes and involved in clearing away the potentially toxic buildup of Alzheimer’s proteins in the brain.

Moreover, Alzheimer’s patients who carry a genetic variant that reduces YKL-40 levels maintain their cognitive faculties longer than people without the variant.

The findings suggest that YKL-40 is a possible link between body clock dysfunction and Alzheimer’s and that therapies targeting the protein may slow the course of the disease.

The study is published in Science Translational Medicine. One author is Erik Musiek, MD, Ph.D.

Our daily rhythms are set by a master clock in the brain that is driven by the day and night cycle. Each cell also maintains its own internal clock, pegged to the master clock.

Fractured sleep, daytime sleepiness, and other signs of disturbance in one’s circadian rhythm are common complaints of people with Alzheimer’s disease, and the problems only get worse as the disease progresses.

But the reason for the link between Alzheimer’s and circadian dysfunction is not well understood.

Previous studies had discovered that high levels of YKL-40 in the cerebrospinal fluid are a sign of Alzheimer’s.

In the study, the team took Alzheimer’s mouse models prone to developing amyloid plaques and crossed them with genetically modified mice that lack the gene for YKL-40, or with unmodified mice for comparison.

Once the mice were eight months old—elderly, by mouse standards—the researchers examined the animals’ brains.

The amyloid-prone mice without YKL-40 had about half as much amyloid as those that carried the gene.

Amyloid plaques normally are surrounded by immune cells called microglia that help keep the plaques from spreading.

In the mice that lacked YKL-40, the microglia were more plentiful and more primed to consume and remove amyloid.

The team then analyzed genetic data from 778 older people.

They found about a quarter (26%) of them carried a genetic variant that reduces levels of YKL-40. Cognitive skills declined 16% more slowly in these people with the variant.

These findings suggest that in Alzheimer’s, protein YKL-40 is bad. People who have less of it fare better.

The team says if scientists could design a therapy to lower YKL-40, it might help the microglia remove more amyloid and maybe slow the progression of the disease.

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