Research suggests the clearance of protein linked to Alzheimer’s disease is controlled by the body’s circadian cycle. This connection to the ability of immune system to destroy Alzheimer’s-related protein appears to oscillates with daily circadian rhythm and this finding could assist with recommendations for reducing the risk of the onset of Alzheimer’s disease.
The research comes from Rensselaer Polytechnic Institute and it focuses on the importance of healthy sleep habits as one of the measures to prevent the protein Amyloid-Beta 42 (AB42) from forming clumps in the brain. The protein is connected to the production in the risk, onset, and progression of the neurodegenerative disorder Alzheimer’s disease.
The circadian system is composed of a ‘clock proteins’ that anticipate the day/night cycle by triggering daily oscillations in the levels of enzymes and hormones. These have a significant bearing upon physiological parameters like body temperature and the immune response. The new findings add to the growing research around how the disruption of the circadian system is associated with diseases like diabetes, cancer, and neurodegenerative diseases.
Specific to Alzheimer’s, the researchers have noted how oscillations in enzymes that help to make two proteins macrophage cell surfaces: heparan sulfate proteoglycan and chondroitin sulfate proteoglycan. These have been shown to play a role in regulating clearance of AB42.
In particular, the studies show how the amount of AB42 ingested by healthy macrophages oscillates with a daily circadian rhythm. When this is disruption, such as through sleep deprivation or shift work, then the amount of AB42 ingested is lowered.
The researchers write: “What’s clear is that this is all timed by the circadian clock. 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.”
They add: “In theory, if we could boost that rhythm, perhaps we could increase the clearance of AB42 and prevent damage to the brain.”
The new finding opens a path to potential Alzheimer’s therapies. The findings appear in the journal PLOS Genetics, titled “Circadian control of heparan sulfate levels times phagocytosis of amyloid beta aggregates.”
