Key to preventing Alzheimer’s may be getting a better-quality sleep

TROY, N.Y. — A good night’s sleep every night may be the best way to prevent the onset of Alzheimer’s disease, a new study reveals. Researchers from the Rensselaer Polytechnic Institute say a person’s circadian rhythms play a key role in wiping out a protein that clumps up in the brain and eventually causes dementia.

Specifically, the study found that healthy sleep habits and avoiding sleep interruptions help the brain clear out the protein Amyloid-Beta 42 (AB42). In Alzheimer’s patients, previous studies have revealed that increasing levels of AB42 “clumping up” in the brain is one of the tell-tale signs of the disease’s onset. The new report found that maintaining a healthy circadian cycle boosts the immune system’s ability to flush harmful proteins from a person’s system.

“Circadian regulation of immune cells plays a role in the intricate relationship between the circadian clock and Alzheimer’s disease,” says Jennifer Hurley, an expert in circadian rhythms, and associate professor of biological science, in a university release. “This tells us a healthy sleep pattern might be important to alleviate some of the symptoms in Alzheimer’s disease, and this beneficial effect might be imparted by an immune cell type called macrophages/microglia.”

“This insight reveals a new mechanism and path to treatment of neurodegenerative diseases like Alzheimer’s through an interdisciplinary approach, and is emblematic of the CBIS strength in research and discovery and provides a new angle to human health and well-being,” adds Deepak Vashishth, director of the Rensselaer Center for Biotechnology and Interdisciplinary Studies.

What makes the circadian cycle so important?

These rhythms, which regulate our body functions during the entire 24-hour cycle, contain a core set of “clock proteins” which anticipate both day and nighttime activities. This causes the daily swaying back and forth in enzyme and hormone levels. Simply put, the circadian cycle tries to prepare the body for the times it should normally be awake and when it should be asleep.

All of this leads to different immune responses and even changes in body temperature throughout the day. Disruptions in these rhythms, however, can increase the risk of both mental and physical illness — including increasing the risk of diabetes, certain cancers, and dementia.

The new study found that macrophages — immune cells that destroy unwanted material in the body — help clean out AB42 in the brain. The macrophages actually ingest this protein in a process scientists call phagocytosis.

In earlier research, Dr. Hurley’s team found that levels of macrophage RNA and proteins oscillate according to the daily circadian rhythm. In the new study, they found fluctuations in certain enzymes which help create two proteins on the surface of the macrophage cells — heparan sulfate proteoglycan and chondroitin sulfate proteoglycan. Researchers say having less of both of these proteins contributes to macrophages being able to clear out AB42 from the brain.

Less protein leads to better Alzheimer’s defense

In experiments to test the link between the circadian cycle and these cell surface proteoglycans, study authors discovered that the amount of AB42 healthy macrophages can ingest sways with a patient’s daily circadian rhythm. The team did not find the same pattern in immune cells that did not have this internal clock to regulate them.

Moreover, in healthy macrophage cells running on the proper circadian cycle, both proteoglycans dropped to their lowest levels — leading to the immune cells doing a better job of cleaning out harmful, Alzheimer’s-causing proteins.

“What’s clear is that this is all timed by the circadian clock,” Dr. Hurley explains. “When there’s a lot of these cell surface proteoglycans, the macrophages don’t ingest the AB42. We’re not certain why that would be, but there is definitely a relationship.”

“In theory, if we could boost that rhythm, perhaps we could increase the clearance of AB42 and prevent damage to the brain,” Dr. Hurley concludes.

The study is published in the journal PLOS Genetics.

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