Protein plaques associated with Alzheimer’s disease may build up in the brain if sleep is disrupted because this affects cells that normally destroy them, according to a study involving mouse immune cells
The immune system may remove the protein plaques in the brain associated with Alzheimer’s disease on a circadian schedule and this could be affected by sleep loss, a study involving mouse cells suggests.
The circadian schedule is an internal clock that controls sleep and a vast array of other bodily processes on a roughly 24-hour cycle. Doctors have long observed that people with Alzheimer’s disease have sleep disturbances and circadian disruption, but it remains unclear the extent to which this disruption could be a cause for the condition itself.
Now, Jennifer Hurley at the Rensselaer Polytechnic Institute in New York and her colleagues have found one possible mechanism by which beta-amyloid plaques, which are found in high numbers in the brains of people with Alzheimer’s, could be related to sleep. Hurley and her team think the plaques are cleared away by macrophages, immune cells that destroy foreign material, according to the body’s daily rhythms.
The researchers arrived at this conclusion following lab studies. They extracted macrophages from mice bone marrow and fed them beta-amyloid plaques, treated with fluorescent tags, at different times of day. By counting the plaques the cells had consumed, the researchers could map out the circadian rhythms of the macrophages.
Hurley and her team also identified a class of circadian-controlled proteins involved, called heparan sulphates, which Hurley thinks may signal to the macrophages when to clear away the plaques. These proteins control many processes, but are typically associated with inflammation.
Understanding the timing and mechanisms of the macrophage plaque-clearing process could lead to new treatments for some of the symptoms of Alzheimer’s disease, says Hurley. The build-up of beta-amyloid plaques rises and falls in healthy brains, but this oscillation can stop as people get older, leading to more plaques. “Since we know that this oscillation goes away with time, perhaps we can boost that oscillation in Alzheimer’s patients,” says Hurley.
One thorny question in the field of Alzheimer’s research is whether the beta-amyloid plaques are a cause or symptom of the disease. Some treatments that clear away the plaques don’t appear to alleviate the disease symptoms, which has puzzled researchers. But Hurley thinks her team’s finding could have implications regardless, as macrophages also remove other proteins associated with Alzheimer’s, like twisted tau fibres. “If macrophages take up and clear [beta-amyloid plaques], they probably take up tau in the same way,” she says.
Whatever the exact role beta-amyloid plaques play in the disease, plaque build-up is a risk factor for Alzheimer’s.
“[The study] emphasises the important role of circadian rhythms in [beta-amyloid] clearance,” says Russell Foster at the University of Oxford. “Therefore, it’s really important to maintain robust circadian rhythms. Individuals like night-shift workers or our front-line staff will be at greater risk.”
Journal reference: PLoS Genetics, DOI: 10.1371/journal.pgen.1009994
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