“I am not completely satisfied with it,” says Van Olst after her trial defense. “In my head, things often have to be perfect.” Her jet lag must have something to do with it: Van Olst has just returned from the United States, where she is doing a postdoc at Northwestern University in Chicago. But despite the jet lag and the many scientific terms – from T cells and microglia to the blood-brain barrier and tau proteins – Van Olst is able to explain her research clearly. Her main discovery? “Immune cells in our blood contribute to the course of Alzheimer’s disease. The immune system outside our brain can therefore be an important target for new therapies.”
‘Working with a different type of cells felt like cheating’
Spider-like cells
To make this discovery, we have to go back to Van Olst’s bachelor’s research in Groningen, when she studied immune cells in the brain. “Those cells are called microglia and are really my passion, haha. I find it super interesting that your brain has its own immune system. For example, did you know that about ten percent of your brain cells are immune cells? Microglia are a type of spider-like cells that continuously scan their environment for pathogens with their legs. In addition, they communicate with nerve cells and help create new memories.”
Multiple sclerose
During her PhD, Van Olst not only conducted research into Alzheimer’s, but also into the brain disorder multiple sclerosis (MS). To do this, she examined brain tissue from deceased donors. She discovered, among other things, that inflammation in the meninges is involved in the course of the disease in MS patients and that microglia play an important role in this. Van Olst then concluded that immune cells are crucial in several brain diseases.
Immune cells in brain and blood
During her bachelor’s and master’s, Van Olst studied these immune cells in brain disorders such as Alzheimer’s and schizophrenia. During her PhD research at the VU, Van Olst also looked at the immune system in the rest of our body, which consists of a collection of different immune cells. Previously, the belief was that the immune system in the brain is isolated from the rest of the immune system, until scientists recently proved otherwise. Van Olst therefore wanted to know: do immune cells in our blood perhaps have something to do with brain diseases? “Actually, I didn’t want to work on cells other than microglia, it felt a bit like cheating,” she laughs. “But now that I’ve worked on that for five years, I realize that the immune cells in your brain don’t do it alone. They are part of a huge army of immune cells scattered throughout your body. Recent research by other scientists confirms this picture.”
‘Perhaps we can prevent brain aging by keeping the immune system young’
Friend or enemy?
In a study, Van Olst showed that substances from the blood of old mice can accelerate the aging of the immune system in young mice. This, in turn, can have harmful effects on brain cells. “So maybe we can fight brain aging by keeping immune cells in the blood young.”
In another experimental model of Alzheimer’s disease, Van Olst showed that immune cells in the brain broke down parts of brain cells that are important for making memories. According to Van Olst, this is an indication that the immune system may contribute to memory loss in people with Alzheimer’s.
Overtired immune cells
Van Olst also did blood tests on Alzheimer’s patients. “I found that a higher proportion of their immune cells were overtired than in healthy people, even in patients with mild memory complaints. This means that the immune system outside the brain may play a role in the early stages of Alzheimer’s disease and could therefore be a target for new therapies.”
According to van Olst, this also shows how important it is to keep your immune system healthy. “Hopefully, my results can lead to new immune therapies that can reverse the loss of brain cells.”
Previous research has shown that certain genes increase the risk of Alzheimer’s in some people. Van Olst discovered that something strange is going on with immune cells from Alzheimer’s patients who were carriers of one of these genes. “These immune cells were more reactive and had a different fat metabolism. We are now further investigating whether and how this contributes to Alzheimer’s disease.”
From competitor to colleague
She is conducting this research as a postdoc in Chicago, in the group of assistant professor David Gate. And that is no coincidence: “Many people do research on microglia, but hardly anyone looks at the interaction with the blood. David has conducted groundbreaking research into this in recent years, including in people with Alzheimer’s. I thought: he does what I want to do and I want to learn from him. And the good thing is: we are no longer competitors, but colleagues.”
Van Olst’s thesis is here to find.
