Tell us about your research!
The glymphatic system is a physiological formation that cleans waste products from the brain via the cerebrospinal fluid (CSF) while we are sleeping. It was characterized for the first time as late as 2012, implying that there is still a lot left to discover in this field. What makes this especially interesting is that this system also is responsible for about 25 % of the amyloid clearance. My contribution has been to develop a large animal model to study how this process works. Once the porcine model was in place, we wanted to elucidate how the glymphatic system clears amyloid from the brain and what can go wrong in Alzheimer’s disease (AD).
Why is your project important? (What difference could it make for patients?)
If we can understand in greater detail how the glymphatic system works, then it might be possible to boost it or prevent malfunctioning in individuals at risk for example proteinophaties in the future. This could possibly be achieved with designed drugs or lifestyle interventions, such as exercise or getting better sleep. If young people knew more about the importance of sleep in the greater perspective of their lifespan, I think there is much to win at a public health level. Each data point we generate is a step towards that deeper understanding, a higher truth. And to use more human-like animals such as pigs instead of rodents will most likely increase the chances for successful future clinical translation.
What is the major difference between rodents and pigs regarding the glymphatic system? Why are pigs better?
Just like the human brain, the brain of pigs is gyrencephalic in structure. This means that the cortex, the most superficial part of the brain, is folded. And this folding into sulci provides highways for the CSF to get deep into the brain and assure a more efficient clearance. In contrast, rodents have lissencephalic brains with a smooth, unfolded cortical anatomy, making them very different from humans in this perspective.
Some scientists claim that the assumption that glymphatic clearance would play a substantial role in Alzheimer’s pathology is only due to a hype. Is there any evidence of glymphatic dysfunction in patients with Alzheimer’s disease?
Well, it has been seen that there is a decline in glymphatic function with ageing, but that is nothing unique to this system, as most bodily functions seem to worsen with age. Clinical evidence is so far scarce. The reason is that adding a CSF tracer in living humans is invasive, so for ethical reasons, this is nothing you do in AD patients. However, there have been studies with comorbid patients having mild cognitive impairment revealing that they have delayed clearance of such a CSF tracer. And a brand new human postmortem study shows that AD brains had reduced polarization of the AQP4 water channel which is pivotal for glymphatic function. Additionally, from my work I pigs, we know there is an interaction between the glymphatic system and amyloid, when the protein is acutely introduced into the CSF.
So, based on what you know about the importance of sleep for the glymphatic function, do you live as you learn?
In general, yes. I try to always get eight hours of sleep and I have more or less the same routine for going to sleep on weekdays. Of course, PhD life also includes the joy of defence parties, so those nights are accepted for a greater good J
How did you end up at MultiPark?
Six years ago, I didn’t know anything about LU. During my master’s education the discovery of the glymphatic system was relatively new, and something that made me curious. Also, I have Danish ancestry and always felt drawn to Scandinavia. So I got in touch with Iben Lundgaard, an expert in the field, and when she started her lab, I came here to pursue a PhD.
What did you like the most during your thesis work at MultiPark?
MultiPark arranged an inspiring panel discussion during one of their retreats. Getting an idea of different group leaders within the organization was highly valuable to me as a PhD student. As many other PhD students already mentioned, the travel grants and graduate school lunch seminars are great initiatives for young researchers to disseminate their research, first internationally and then locally.
What have been the most challenging during your PhD?
Setting up a brand new modelling system is not an easy task. But in comparison with dealing with the Swedish migration system, I must say that it was a walk in the park. Honestly, I would not recommend any non-European student to pursue a PhD in Sweden, which I find sad, because there have also been good moments here, but they simply do not outweigh the obstacles. Since I come from South Africa, it has been a never-ending story of going back and forth to renew my residence permit, months of being stuck in Sweden, and even moments when I have been forced to leave, and I know similar stories from others at BMC. Several times, this system left me with no prediction and no control over whether I could complete my projects or not. This is not how you should treat people wanting to come and contribute to developing your research. I believe that Sweden has much to gain from optimizing how this is handled. It not only creates obstacles for ambitious people in their careers but also prevents Sweden from taking advantage of their competences to develop world leading research and innovation.
And the most rewarding?
Having the possibility to join Iben at the time while she was setting up her research line here at LU has been truly stimulating. I have had the pleasure of taking part in the whole journey from where we didn’t have an established model until now when we have started to make discoveries about how the glymphatic system works in large mammals.
What advice do you want to give to new PhD students?
Figure out early what the requirements are for getting the PhD. Then, talk with your supervisor and start with completing a fairly simple project which you can publish early on as a first author. Like that, you reduce the stress. Thereafter, you can enjoy digging into more advanced long-term projects, which may generate a higher impact paper that will benefit your career and be useful for your research group.
What happens after your defence?
I will stay in Lund for a postdoc, but I will move over to work more on the clinical side with lung transplantations in pigs in Sandra Lindstedt’s group.