Alzheimer’s: Addressing sleep disturbance may alleviate symptoms
Dementia is one of the leading causes of death worldwide. The most common form, Alzheimer’s disease affects 1 in 9 people aged 65 and over in the United States and 1 in 14 in this age group in the United Kingdom.
A feature of AD is a disruption in circadian rhythms, the daily physical, mental, and behavioral changes that control our sleep and wakefulness. People can experience sleep disturbances, which are associated with more severe symptoms, years before receiving an AD diagnosis.
They carried out their research in a laboratory, using cells derived from mouse white blood cells. The researchers identified a molecular mechanism that may be responsible for the connection between AD and circadian rhythms.
Alzheimer’s is a neuroinflammatory disease characterized by the buildup of beta-amyloid. The most damaging of these is beta-amyloid 42 (Aβ42). The proteins form plaques that collect between neurons and disrupt cell function.Scientists believe the growth of amyloid plaques is a crucial step in the development of AD.
Immune cells called microglia play a role in clearing amyloid plaques. This process, called phagocytosis, is essential for maintaining healthy neurons. Using mouse cells, the researchers found that phagocytosis changes throughout the day and night. When phagocytosis is interrupted, for example, by sleep disruption, Aβ42 builds up.
People with AD experience a range of symptoms, including memory loss, confusion, delusions, and impulsive behavior. There is a strong association between the buildup of plaques and the development of AD, but it is not yet clear whether the plaques cause the symptoms.
Scientists think that amyloid plaques accelerate the development of tau tangles, which further damage neurons. Many Alzheimer’s symptoms are due to neuronal damage.
Immune cells in the brain are known to clear amyloid, which is one of the hallmarks of Alzheimer’s. The researchers found that the timing of expression of certain molecules on immune cells helps time the uptake and clearance of amyloid.
Decreased plaque clearance
The researchers found that molecules on the cell surface called heparan sulfate proteoglycans were key to the phagocytosis of Aβ42.
These heparan molecules respond to circadian rhythms, with the number of molecules fluctuating during the 24-hour cycle. The researchers found that when heparan levels were higher, phagocytosis of Aβ42 decreased.
Therefore, the sleep disruption that is common in AD may affect heparan levels. This, in turn, affects the accumulation of amyloid plaques. The researchers suggest that controlling circadian rhythms may help control inflammatory conditions such as AD.