Study finds link between Alzheimer’s and circadian clock

Research raises hopes for new therapies that could help tackle disease and symptoms

theguardian \ Ian Sample Science editor @iansample

People who develop Alzheimer’s disease can experience sleep disturbances years before the condition takes hold, but whether one causes the other, or something more complex is afoot, has always proved hard for scientists to determine.

Now, researchers in the US have shed light on the mystery, in work that raises hopes for new therapies, and how “good sleep hygiene” could help to tackle the disease and its symptoms.

The findings show that humans’ 24-hour circadian clock controls the brain’s ability to mop up wayward proteins linked to Alzheimer’s disease. If the scientists are right, the work would explain, at least in part, how disruption to circadian rhythms and sleep disturbances might feed into the onset and progression of Alzheimer’s disease, and how preventing such disruption might stave off the condition.

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“Circadian disruption is correlated with Alzheimer’s diagnosis and it has been suggested that sleep disruptions could be an early warning sign of Alzheimer’s disease,” said Dr Jennifer Hurley, who led the research at Rensselaer Polytechnic Institute, in New York.

Alzheimer’s takes hold when connections are lost between nerve cells in the brain. The disease is progressive and linked to abnormal plaques and tangles of proteins that steadily build up in the brain. The disease is the most common cause of dementia and affects more than half a million people in the UK, a figure that is set to rise.

To keep the brain healthy, immune cells called microglia seek out and destroy troublesome proteins that threaten to accumulate in the brain. One type of protein targeted by the cells is called amyloid beta, a hallmark of Alzheimer’s.

Writing in the journal Plos Genetics, Hurley and her team describe how they found a daily rhythm in microglia, which drove regular waves of protein-clearing. When the cells lost their circadian rhythm, the clearing routine faltered.

“The disruption of the proper timing of amyloid beta clearance could be one of the reasons we see an increase in plaques that form in the brain during Alzheimer’s disease,” Hurley said.

While sleep disturbances often arise before Alzheimer’s disease, Hurley and many other scientists suspect there is a complex interplay between the two. Disrupting sleep and circadian rhythms allowed amyloid beta to build up, Hurley said, but this in turn damaged brain cells that ran the circadian clock, causing further accumulation of amyloid beta.

“We have known for a while that there is a rhythm in the clearance of amyloid beta in the brain,” Hurley said. “As we age, and more so in Alzheimer’s patients, this rhythm disappears. This loss could lead to the increase of amyloid beta in the brain.”

But the findings point to therapies that could potentially reduce the risk of Alzheimer’s or lessen the severity of the symptoms. Hurley said it may be possible to stimulate the brain’s ability to clear out amyloid beta with simple interventions, such as exposure to light, or via more sophisticated therapies that boost the activity of the immune cells.

“Taking care of our sleep or circadian rhythms – sometimes called good sleep hygiene – may be able to reduce amyloid beta burden over our lifespan,” she said. “Reducing amyloid burden could mean a reduction in Alzheimer’s symptoms or a delay in the onset or progression of the disease.”

Topics: Alzheimer’s\Health\Sleep\Medical research\Health & wellbeing\news