Nordic centre to strengthen research into the glymphatic system
The Lundbeck Foundation has awarded DKK 78 million to a pan-Nordic centre that will focus on research into the glymphatic system — popularly known as the brain's dishwasher. The goal is for researchers, within five years, to have developed a diagnostic tool that can assess the brain's ability to cleanse itself, and to be ready to conduct clinical trials with a new drug against dementia.
By Anne Westh
"It is important to sleep, because you need to cleanse your brain."
That is what Professor Maiken Nedergaard used to tell her children when they were young. And in its simplicity, it also captures the message of her extensive research into the glymphatic system: the brain needs a good night's sleep to be flushed clear of waste products so that it is ready for the next day's tasks.
Now Maiken Nedergaard from the University of Copenhagen has received a grant of DKK 78 million from the Lundbeck Foundation to build the Nordic Center for Glymphatic Biology, where she and colleagues from Sweden, Norway and Finland will develop research into the glymphatic system over the next five years. And, not least, train the brain researchers of the future so that they are ready to drive the field forward.
The brain is flushed clean at night
The name 'glymphatic system' is a combination of the words glia (the support cells of the nervous system) and the lymphatic system (the body's cleansing system). The brain does not have classical lymphatic vessels within its tissue, but has developed an alternative system for removing waste products. This system is called the glymphatic system because it performs a function similar to that of the lymphatic system, but is organised differently and depends on glial cells.
It is Maiken Nedergaard's research that has shown that the brain has its own cleansing system — often popularly referred to as the brain's dishwasher. During sleep, cerebrospinal fluid circulates through the brain along the blood vessels and flushes waste products away from nerve cells. These waste products are then transported out of the brain and into the lymphatic system.
This process is most active during sleep and helps ensure that the brain can function optimally, so that one wakes up fresh and ready for a new day.
"Getting good sleep throughout life is important, because otherwise you increase the risk of developing dementia. One of the reasons why many older people develop dementia is that with age, the brain becomes less efficient at getting rid of waste products," says Maiken Nedergaard.
Scandinavian researchers are the best
The researchers who have joined forces to build the Nordic Center for Glymphatic Biology will work with the glymphatic system using different research techniques that together span the full range from basic fundamental research to trials in humans. The focus is particularly on how the function of the glymphatic system can influence small vessel disease, which is the second most important cause of dementia.
At the University of Copenhagen, Maiken Nedergaard's research group will work with mouse studies in which they will seek to identify molecular mechanisms that can regulate glymphatic flow and perhaps later increase the rate at which waste products are removed from the brain.
Professor Per Kristian Eide and Associate Professor Geir Ringstad from Oslo University Hospital will use an invasive MRI scanning technique to investigate glymphatic flow in the brains of people with vascular disease. At the University of Oulu in Finland, Professor Vesa Kiviniemi will use a special non-invasive MRI technique, MREG, to examine how fluid moves in the glymphatic system in people who have or are at risk of developing vascular disease.
Building on this, Professor Gitte Moos from Rigshospitalet will verify the results using a SPECT scanner for the same purpose. In addition, Associate Professor Iben Lundgaard from Lund University in Sweden will conduct experiments on pigs focused on methods for flushing the glymphatic system.
"The centre brings together internationally recognised researchers with expertise in the glymphatic system. For some reason, Scandinavia has the best researchers in the field, and by establishing the centre we can work together and more quickly translate our knowledge into clinical use," says Maiken Nedergaard.
Sleep can prevent dementia
Over the course of the centre's five-year funding period, the plan is to develop a diagnostic platform capable of producing a so-called glymphogram — an MRI scan that can establish the status of the glymphatic system.
"We can probably, within a relatively short timeframe, establish a clinical platform so that middle-aged people can receive a scan that within 20 minutes can tell them whether their brain's dishwasher is functioning well. The methods already exist at the experimental level, and I expect that in the coming years a straightforward solution will be developed and validated that can also be used at smaller hospitals," says Maiken Nedergaard.
As part of the grant, Maiken Nedergaard's laboratory will also identify molecular mechanisms that can serve as a basis for developing new drugs or testing existing drugs that can improve the cleansing process carried out by the glymphatic system. These drug candidates will subsequently be tested both on pigs and in humans by the other research groups at the centre. Maiken Nedergaard hopes this will pave the way for developing a new drug that can prevent dementia.
It would be fantastic if it became possible to offer preventive treatment to middle-aged people who are at high risk of developing dementia. Because by the time a family member notices that a relative has become demented, it is essentially too late to treat, because the brain has already sustained damage by that point.
Professor at the University of Copenhagen
"It would be fantastic if it became possible to offer preventive treatment to middle-aged people who are at high risk of developing dementia. Because by the time a family member notices that a relative has become demented, it is essentially too late to treat, because the brain has already sustained damage by that point."
Maiken Nedergaard describes it as a "huge problem" that we are not better at treating dementia today, because an ageing population will inevitably lead to a greater prevalence of dementia. At the same time, she believes that the new drugs currently available for the treatment of, for example, Alzheimer's disease are focused in the wrong direction.
"The new drugs work by removing a single waste product from the brain — amyloid. But ageing is far from that simple, and there are many waste products and processes that are set in motion by ageing. We need to prevent amyloid and other waste products from accumulating before nerve cells sustain damage," says Maiken Nedergaard.
Young researchers must be supported
In addition to advancing research into the glymphatic system to the next level, the centre also aims to train young researchers in the field. Among other things, PhD students and postdocs at the centre will meet one day before the senior researchers when the centre holds its annual meeting, so that they can exchange ideas and build networks on their own terms.
"We will focus on how we as experienced researchers can support younger researchers who are on their way to becoming independent. So when the grant ends in five years, I hope the younger researchers will be self-sufficient and able to build their own networks that can drive the research field forward," says Maiken Nedergaard.
The glymphatic system was discovered and described by Professor Maiken Nedergaard, for the first time in 2012. The system cleanses the brain of waste products during sleep, and is popularly referred to as 'the brain's dishwasher'.
If the glymphatic system functions poorly, waste products accumulate in the brain and the risk of developing dementia increases.
