Alzheimer's Disease: A Link With Respect To The Circadian Rhythm?

The links between sleep and the onset of Alzheimer's disease are getting closer and closer.  Long before developing Alzheimer's disease, some patients already have sleep problems that scientists are trying to better understand.  Until now, it is impossible to know if it is the sleep problems that have an influence on the development of the disease or if it is the disease that causes these sleep disorders.  This time, new findings published in Plos Genetics hint that preserved sleep could be a way to fight Alzheimer's.  The circadian clock, our 24-hour biological clock, may well control the mechanism in the brain that eliminates disease-causing proteins.

The circadian rhythm consists of a system of proteins that anticipate the cycle of day and night by modifying the levels of enzymes and hormones in the body, which affects several physiological parameters, such as body temperature or even immune response. Research has already shown that disrupting the circadian rhythm is associated with the onset of diseases such as diabetes or cancer. It would also have a role in Alzheimer's disease.  The latter is characterized by the appearance of amyloid plaques, called AB42, which accumulate in the brain. These proteins aggregate around the neurons and then prevent them from functioning properly. To limit the number of these AB42s in the brain, microglia, immune cells from the macrophage family, are responsible for identifying and destroying unwanted molecules. They are the ones that get rid of AB42 in the brain by phagocytizing them, that is to say by absorbing them.  

Immune cells that follow our circadian rhythm

In their study, they worked on a molecular mechanism potentially responsible for this link between Alzheimer's disease and circadian rhythms. They measured the activity of immune cells responsible for eliminating so-called beta-amyloid proteins that accumulate in the form of plaques in the brains of people with Alzheimer's disease.  Using cells grown in the lab, they discovered that they shed amyloid-beta protein in a daily cycle, controlled by circadian rhythms. When the cells no longer followed these rhythms, the cycles of elimination disappeared. According to their findings, this is linked to molecules of another protein, called heparan, which is found on the surface of these cells. Its functioning is also based on circadian rhythms, and previous studies have shown that it is involved in the elimination of beta-amyloid proteins.

 A new avenue of treatment

If this study provides information on the origins of the disease and certain symptoms (because sick people often suffer from sleep disorders several years before the onset of the disease), it also offers new avenues for reflection concerning its treatment.  "Understanding how our circadian rhythms can regulate cell surface heparan levels to control beta-amyloid accumulation may lead to the development of chronic therapies that alleviate symptoms of Alzheimer's disease as well as other inflammatory diseases.  ", says Jennifer Hurley, lead author of this study.  The idea would be to restart the daily cycle of amyloid-beta protein elimination to prevent the disease from progressing or getting worse.

References

1. Rensselaer Polytechnic Institute. "Clearance of protein linked to Alzheimer's controlled by circadian cycle: Ability of immune system to destroy Alzheimer's-related protein oscillates with daily circadian rhythm." ScienceDaily. ScienceDaily, 10 February 2022. <www.sciencedaily.com/releases/2022/02/220210154215.htm>. 

2. Campbell, Molly. “Circadian Control of Immune Cell Linked to Clearance of Alzheimer’s Protein.” Proteomics & Metabolomics from Technology Networks, 10 Feb. 2022, www.technologynetworks.com/proteomics/news/circadian-control-of-immune-cell-linked-to-clearance-of-alzheimers-protein-358437.