A new brain imaging study in mice suggests that sleep may not help flush out the brain of toxins and everyday waste products, challenging what scientists have called a 'Nobel-prize winning idea' of neuroscience.
"The field has been so focused on the clearance idea as one of the key reasons why we sleep, that we were very surprised to observe the opposite in our results," says Nick Franks, a neuroscientist at Imperial College London (ICL) who co-led the study.
Sleep, although mysterious, has many possible benefits, from consolidating memories to improving mental health that we shouldn't dismiss.
But hot on the heels of the (now contested) amyloid hypothesis, which describes how clumps of proteins build-up in the brains of people with Alzheimer's disease, sleep is thought to help the brain clear away the day's waste.
Decades of research have also linked sleep to protein clearance and Alzheimer's disease. As a result, sleep has been singled out as a key modifiable risk factor for Alzheimer's, the most common form of dementia, although the relationship is complicated: poor sleep could be a contributing factor to Alzheimer's disease or a symptom of it.
One animal study certainly isn't going to overturn mountains of research linking sleep, proteins, and neurodegenerative disease, but given those complexities, it might prompt further investigations.
The researchers injected a fluorescent dye into the brains of mice, watched it spread, and measured the rate of clearance when the animals were awake, asleep, and under anesthetic.
They cross-checked their imaging results with further measurements in 'brain phantom' gels made of agarose and slices of mouse brain tissue, collected at different time points.
"Our results challenge the idea that the core function of sleep is to clear toxins from the brain," the researchers write in their paper.
"We found that the rate of clearance of dye from the brain was significantly reduced in animals that were asleep, or under anesthetic," Frank adds.
Previous research has established that using tracer dyes is a fair method for estimating how fast fluid flows through the brain, a process that we assumed washed away proteins and other waste products.
However, while the bulk flow of fluid might increase through the brain during sleep, this does not mean the brain is clearing the fluid of waste products. Some findings support the idea, while others, like the current results, challenge it.
What's more, the size of the molecules in the fluid might affect how quickly they move through the brain, and via which channels. The different fluorescent dyes used in this study weighed far less than clumps of misfolded proteins that accumulate in Alzheimer's disease, Parkinson's and other neurodegenerative diseases.
The study was also primarily concerned with bulk fluid flow through the brain, what's known as the glymphatic system, when other mechanisms – namely an intracellular 'garbage disposal' system – play a big role in mopping up lumpy proteins.
Nevertheless, the results are worth considering: The brains of sleeping mice cleared the green fluorescent dye 30 percent slower than awake animals, and anesthesia slowed brain clearance by 50 percent.
"As yet, we do not know what it is about these states that slows down the removal of molecules from the brain [via the glymphatic system]," Franks says. "The next step in our research will be to try to understand why this occurs."
Despite the findings, the researchers don't say they detract from the importance of sleep. Up to 44 percent of Alzheimer's disease patients have sleep disturbances, as do 90 percent of those with dementia with Lewy bodies or Parkinson's disease.
"Disrupted sleep is a common symptom experienced by people living with dementia, however we still do not know if this is a consequence or a driving factor in the disease progression," says ICL molecular neuroscientist and study author Bill Wisden.
"It may well be that having good sleep does help to reduce dementia risk for reasons other than clearing toxins."
The study has been published in Nature Neuroscience.