Sleep disruption in Alzheimer’s – the typical dozing in the day and inability to sleep at night – is caused by the biological clock detaching from the sleep-wake cycle that it normally regulates, according to new research at Cambridge University, UK.
The poor sleep routine of Alzheimer’s has not before been fully understood. Scientists unable to pinpoint the direct cause assumed that the biological clock simply stopped ticking.
The findings, however, published in the journal Disease Models and Mechanisms, show that the clock continues to tick but is “ignored” by the brain. In the study, fruit flies were used – a key species for studying Alzheimer’s. Taking a group of healthy flies and a group with the Alzheimer’s protein, researchers studied the sleep patterns in the flies as well as the inner workings of their biological clocks.
Studying the sleep pattern
By fitting a small infrared beam to the glass tubes housing the flies, the researchers monitored the sleep-wake patterns of both sets of flies. Similar to the movement sensors in burglar alarms, when the flies were awake and moving, the infrared beam was broken and a instance of “non sleep” was recorded.
Studying the biological clock
To study the flies’ biological clocks, the protein luciferase – an enzyme that emits light – was attached to one of the proteins that forms part of the biological clock. This allowed researchers to monitor the internal clock as the glowing protein – rising and falling during the day and night – demonstrated its use. As levels of the protein rise and fall during the night and day, the glowing protein provided a way of tracing the flies’ internal clock. Lead researcher, Dr Crowther said:
This lets us see the brain glowing brighter at night and less during the day, and that’s the biological clock shown as a glowing brain. It’s beautiful to be able to study first hand in the same organism the molecular working of the clock and the corresponding behaviours
Healthy flies were found to be active during the day and to sleep at night. The flies with Alzheimer’s protein however slept and woke randomly. Significantly, the daily patterns of the tagged protein were the same in both the healthy flies and flies with Alzheimer’s protein. This showed that the biological clock still ticks in flies with Alzheimer’s. Dr Crowther added:
“Until now, the prevailing view was that Alzheimer’s destroyed the biological clock. What we have shown in flies with Alzheimer’s is that the clock is still ticking but is being ignored by other parts of the brain and body that govern behaviour. If we can understand this, it could help us develop new therapies to tackle sleep disturbances in people with Alzheimer’s.”
The findings hope to improve the sleep treatment for people with Alzheimer’s, improving the lives of both patients and their carers.
We hope these results can guide further studies in people to ensure that progress is made for the half a million people in the UK with the disease.” Dr Crowther
Image: with thanks to Cris DeRaud of RGB Free Stock