A hallmark of Alzheimer's disease (AD) is the accumulation of damaging amyloid-beta proteins in plaques within the brain. Now, new research in animal models of AD has shown that our circadian clock may help regulate the clearance of amyloid beta proteins by immune cells, underlining the importance of a healthy sleep pattern. Circadian rhythms are physical or biological changes that follow a 24-hour cycle, primarily regulated by light and dark - or sleeping and waking - in humans. These rhythms are collectively known as our body clock, running in the background to perform essential functions that keep our bodies working properly. In a new paper published in the journal PLOS Genetics, a team of researchers led by Dr. Jennifer Hurley of Rensslaer Polytechnic Institute used an animal model of AD to study the link between our circadian clock and amyloid beta proteins in the brain. Noting that AD is associated with sleep disturbances, the researchers looked more closely at immune cells that are responsible for the clearance of damaging proteins such as amyloid beta.
This clearance process, known as phagocytosis, is thought to be regulated by circadian rhythms, which might provide the molecular link between our body clocks and sleep disturbance, and the accumulation of amyloid plaques in the brain in AD. Using a series of experimental techniques, the researchers studied how and when immune cells clear amyloid beta proteins. They found that there was a daily oscillation in amyloid clearance, which fluctuated according to the circadian clock. Closer inspection of the immune cells identified cell surface receptors, called chondroitin sulphate and heparan sulphate proteoglycans (CSPG and HSPG) that fluctuated in time with the circadian clock. Disabling these receptors with an enzyme stopped immune cells from clearing amyloid beta proteins, and increased the accumulation of amyloid plaques, identifying a mechanism that could link circadian clock dysregulation and sleep disturbance in AD.
https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1009994#sec002