Why do people with Alzheimer’s disease have poor sleep?

Our co-founder Yizhou Yu, PhD candidate at Cambridge University explains.

It has long been appreciated that patients with Alzheimer’s disease (AD) have impaired sleep/wake cycles with fragmented and reduced sleep at night. However, no one really understands what the purpose of sleep is and its association with neurodegenerative disorders such as Alzheimer’s disease. Alzheimer’s disease is the most prevalent neurodegenerative disease, affecting more than 1 million people in the UK. Establishing and understanding a link between sleep and Alzheimer’s disease could help us come up with alternative treatments.

To do this, researchers turned to the fruit fly as a model organism. Their results show a bidirectional relationship between sleep and 𝛃-amyloid (A𝛃), a key pathogenic step in the development of Alzheimer’s disease. Not only may A𝛃 accumulation impair sleep, but poor sleep may increase A𝛃 burden. In fact, A𝛃 accumulation causes neurons to be more activated and leads to reduced and fragmented sleep, while chronic sleep deprivation increases increases A𝛃 accumulation. This is a positive feedback loop, whereby sleep loss and neuronal excitation speed up the accumulation of A𝛃, which causes more sleep loss. Importantly, increasing sleep reduces the amount of toxic A𝛃 and breaks this negative loop! This shows that we may be able to treat or slow the progression of Alzheimer’s disease by suppressing A𝛃-induced neuronal toxicity. 

Data in fruit flies suggests that targeting these pathways may be a fruitful approach towards slowing the progression or delaying the onset of this incurable disease. Further research needs to be performed to identify the exact function of sleep. Once this has been established it will help us to understand exactly how disrupted sleep is associated with various neurodegenerative disorders.