On behalf of the research institute Amsterdam Neuroscience, Daphne Naessens has been awarded the AUF Startstipendium 2024 for her research on how the brain keeps itself clean.
What does the cleanup system of the human brain look like?
The brain is the central regulatory organ of the body and plays a crucial role in almost all functions of human life. It is one of the most complex organs in the human body that we do not yet know everything about. For example, while we know much about the brain's excessive deposition of proteins in diseases such as Alzheimer's, relatively little is known about how the brain keeps itself clean.
With her research, Daphne Naessens wants to gain insight into these cleaning processes and investigate how disruptions in these processes contribute to neurological disorders: 'In the case of Alzheimer's disease, a certain protein accumulates between brain cells. There are actually three theories about how this Alzheimer’s protein would accumulate in the brain. One theory is that this protein is overproduced. The other theory is that the local breakdown is impaired and thus not properly cleared locally. The third is that the drainage of this protein actually deteriorates. I want to explore further this last theory by starting with the question: How does the brain remove waste products?
In recent years, research has been conducted mainly in laboratory animals. Here it became clear that especially around the arteries, there are channels of cerebrospinal fluid that are constantly moving along. With the pulsing of those blood vessels, the cerebrospinal fluid in those tubes is constantly moving and the cerebrospinal fluid is washed clean.
Mapping the pathways and mechanisms through which the brain disposes of waste
But how? Naessens: ‘We don't know exactly how that works. Where exactly are these channels located? How are they connected? And how are they connected to the rest of the body? We now have a better understanding of how waste gets into the brain tissue itself, but we don't know how it eventually gets into the lymph nodes, the liver or the rest of the body, for example.’
Naessens' research maps the pathways and mechanisms through which the brain disposes of waste. How do the ducts around arteries interrelate with other drainage systems in the body, such as through the nose, spine or lymph nodes? Instead of working with laboratory animals, Naessens' project focuses on human, deceased donors. Deceased bodies were chosen because they offer more opportunities to look at brains at a detailed level through MRI and CT scans. For this purpose, contrast agents are infused into the brain, which is not possible in living subjects. Deceased bodies also have advantages after the scans: 'The moment the scans are finished, we take out the brains and then we cut them into even smaller slices. And then we really start looking at all those tubes in a lot of detail,' explains Naessens.
Collaboration with other specialties
The greatest challenge lies in collaboration with other specialties. Because the brain and surrounding tissue begin to change rapidly after death, scans and experiments must be performed as soon as possible. This requires close coordination between different departments such as pathology, radiology and anatomy. 'I receive a call from the department of anatomy when someone has come in who fits the profile (including not having died from a neurological condition), then I start calling the department of pathology. Is there someone available to help me? Is the room available and then I also call the department of radiology. Is there anyone who can help me that day with reviewing the scans?
Better understanding of how waste products are cleared from healthy brains
The AUF Startstipendium is an essential step for this research. Although it is not sufficient to fund her entire research, it allows Naessens to lay a good foundation and seek additional funding: 'Among other things, this start-up grant covers the cost of using laboratory supplies and the fees of support staff.' Naessens' research could be groundbreaking on several levels. It contributes to a better understanding of how waste products are cleared from healthy brains. ‘If we understand this system better, it could help treat diseases related to the accumulation of waste products in the brain, such as Alzheimer's and Parkinson's disease.’
Source: AUF Startstipendium