Researchers report that the immune cells responsible for eliminating a key protein that accumulates in the brains of Alzheimer’s patients function according to daily circadian rhythms. The discovery, reported by Jennifer Hurley of Rensselaer Polytechnic Institute and her colleagues in a new study published on February 10and in the review PLOS geneticsprovides a potential explanation for the link between Alzheimer’s disease and disruptions in a person’s sleep cycle.
Alzheimer’s disease is known to be associated with disruptions in circadian rhythms, the 24-hour cycle that controls many aspects of human behavior and physiology. For example, sleep disturbances begin years before the onset of Alzheimer’s disease symptoms and are linked to more severe symptoms and a higher risk of developing the disease.
In the new paper, the researchers investigated a molecular mechanism potentially responsible for the link between Alzheimer’s disease and circadian rhythms. They measured the activity of immune cells responsible for eliminating proteins called beta-amyloid that accumulate in the form of plaques in the brains of people with Alzheimer’s disease. Using cultures of these cells grown in the laboratory, they discovered that immune cells clear beta-amyloid in an oscillating daily cycle controlled by circadian rhythms. However, when the cells lost this rhythm, the daily cycle disappeared. They further established that the underlying cause of this oscillation was changes in the number of molecules of a certain protein, heparan, on the surface of the cell. The protein they identified responds to circadian rhythms and had previously been shown to play a role in clearing amyloid beta proteins.
The new findings reveal a mechanism that links disruption of circadian rhythms to Alzheimer’s disease. The study further highlights the role of immune cells in this relationship. Although further studies are needed, the new findings present the possibility that if daily clearance of beta-amyloid proteins by this mechanism can be maintained, patients may be less likely to develop Alzheimer’s disease and experience symptoms. less severe symptoms.
Hurley adds, “Understanding how our circadian rhythms can regulate cell surface heparan levels to control beta-amyloid accumulation may lead to the development of chronotherapies that alleviate symptoms of Alzheimer’s disease as well as other inflammatory diseases.
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Quote: Clark GT, Yu Y, Urban CA, Fu G, Wang C, Zhang F, et al. (2022) Circadian control of heparan sulfate levels multiplied by phagocytosis of beta-amyloid aggregates. PLoS Genet 18(2): e1009994. https://doi.org/10.1371/journal.pgen.1009994
Author countries: United States, China
Funding: This work was supported by an NIH-National Institute of Biomedical Imaging and Bioengineering Grant U01EB022546 (to JMH) (https://www.nibib.nih.gov/), a grant R35GM128687 from the NIH-National Institute of General Medical Sciences (to JMH) (https://www.nigms.nih.gov/), a National Science Foundation CAREER Award 2045674 (to JMH) (https://www.nsf.gov/), National Institutes of Health grants 1RF1AG069039 (to CW), DK111958, and CA231074 (to RJL) (https://www.nih.gov/), Rensselaer Polytechnic Startup fund (at JMH) (https://www.rpi.edu/), a gift from the Warren Alpert Foundation (to JMH) (https://warrenalpert.org/), and an NIH-National Institute of Aging T32 AG057464 grant (to GTC) (https://www.nia.nih.gov/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Conflict of Interest Statement
Competing interests: The authors have declared that there are no competing interests.
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