Neurodegenerative disorders like Alzheimer’s or Parkinson’s often disrupt sleep, however the new findings give new evidence that sleep loss could play a role in the formation of such disorders.
Senior author of the study, David Holtzman, M.D., explains, “Orexin or compounds it interacts with may become new drug targets for treatment of Alzheimer’s disease. The results also suggest that we may need to prioritize treating sleep disorders not only for their many acute effects but also for potential long-term impacts on brain health.”
Holtzman’s laboratory utilizes a technique called in vivo microdialysis to observe levels of amyloid beta in the brains of mice genetically engineered as a model of Alzheimer’s disease. Amyloid beta is the protein fragment that is the chief component of Alzheimer’s plaques. Researchers monitoring the mice observed brain amyloid beta levels rose and fell in connection with sleep and wakefulness, increasing in the night, when mice are mostly awake, and decreasing during the day, when they are mostly sleeping.
To confirm the link between sleep and amyloid beta levels, researchers used electroencephalography (EEG). The readings allowed researchers to determine when mice were asleep or awake and validated the connection: Mice that were awake longer had higher amyloid beta levels. Depriving the mice of sleep caused a 25 percent increase in amyloid beta levels. Levels were lower when mice were allowed to sleep.
Researchers performed long-term behavioral experiments on the mice and found that three weeks of chronic sleep deprivation accelerated amyloid plaque buildup in the brain. In contrast, when mice were given an orexin receptor inhibiting drug called almorexant, plaque deposition significantly decreased, dropping by more than 80 percent.
Holtzman notes that in addition to the risk of Alzheimer’s increasing with age, the sleep/wake cycle also starts to break down, with older adults getting less and less sleep. Investigators are considering epidemiological studies to determine whether sleep loss in young and middle-aged adults increases risk of Alzheimer’s later in life.