Amyloid Beta Clearance Controlled by Circadian Cycle

Alzheimer’s disease (AD) is a neuroinflammatory disease characterized partly by the inability to clear, and subsequent build-up, of amyloid-beta (Aβ). According to research AD has a bi-directional relationship with circadian disruption with sleep disturbances starting years before the disease onset. 

In a recently published study, researchers found that the phagocytosis of Aβ42 undergoes a daily circadian oscillation, and that healthy sleep habits are of key importance in preventing the protein Aβ42 from forming clumps in the brain. 

Research Results  

The clearance of Aβ42 is essential for a healthy neuronal microenvironment and accumulation of Aβ42 is known to accelerate the development of the symptoms associated with AD. 

The results demonstrated circadian control of the phagocytosis of Aβ42 in murine macrophages. As peripheral macrophages are models for microglia and also migrate to the brain in the later stages of AD, the findings suggest the disruption of the circadian timing of macrophage/microglia phagocytosis may be a vital component in Aβ42 metabolism, which highlights a potential causative factor in the increase in accumulation of Aβ42 in patients with clock/sleep disturbances. 

The researchers noticed changes in enzymes that help to make 2 proteins on the macrophage cell surface, heparan sulfate proteoglycan and chondroitin sulfate proteoglycan, both proteins are known to play a role in regulating clearance of Aβ42.

They found that the peak clearance occurred as production of the proteoglycans was at its lowest level, and removal of the proteoglycans increased ingestion, which suggests that the proteoglycans inhibit Aβ42 clearance.

The team believes that the relationship found could be used to develop new therapies that would increase Aβ42 clearance.

Source:

Clark GT, Yu Y, Urban CA, Fu G, Wang C, Zhang F, et al. (2022) Circadian control of heparan sulfate levels times phagocytosis of amyloid beta aggregates. PLoS Genet 18(2): e1009994. https://doi.org/10.1371/journal.pgen.1009994 

Image from: 

https://sph.umich.edu/pursuit/2020posts/why-sleep-is-so-important-to-your-health.html