Marcel Verbeek has been appointed professor of Translational Research on Neurodegenerative Disorders at Radboudumc / Radboud University. He unravels the causes of brain diseases, such as Alzheimer’s and Parkinson’s. He is also looking for signaling substances in cerebrospinal fluid that can help with an early diagnosis of these disorders.
Marcel Verbeek’s research focuses on the two most common disorders among the elderly in the Netherlands: both Alzheimer’s and Parkinson’s. ‘These appear to be very different diseases, but they have many similarities in the underlying biological processes,’ he says. ‘In both diseases, nerve cells die due to the accumulation of proteins that accumulate in the brain. I’m investigating how that happens. In addition, I look for new substances with which we can detect these diseases at an early stage, so-called biomarkers.’
Verbeek measures these biomarkers in cerebrospinal fluid, also known as liquor. He has been head of the Dutch Reference Laboratory for Liquor Diagnostics since 1999. ‘We look for substances in the cerebrospinal fluid that say something about the state of the brain and that reveal a brain disorder at an early stage. For example, proteins that indicate whether nerve cells and blood vessel cells are still functioning properly, or substances that indicate inflammation. We also look for the first signs of the characteristic protein stack.’
pancakes
By the time the proteins stack up like a stack of pancakes, into cables so large that they can be seen with a microscope, it is too late. Verbeek: ‘Then the damage is irreversible. This process has often been going on for fifteen or twenty years. It starts with normal, healthy proteins that start to fold differently. Those misfolded proteins slowly start to clump together and we try to measure that. That is a promising early biomarker, especially in Parkinson’s disease.’
There is no therapy for Alzheimer’s and Parkinson’s that prevents or cures the condition. So why is an early and accurate diagnosis important? ‘On a global scale, millions of people suffer from these disorders. Partly because there is no good early diagnosis, we are unable to offer customized therapy,’ Verbeek replies. ‘Thanks to new biomarkers, we can better characterize patients and approach them more personally. We can then use a certain treatment or guidance in a much more specific way.’
Role of the intestines
In addition to unraveling processes in the brain itself, Verbeek also studies the relationship between the intestines and the function of the brain. ‘We are seeing more and more evidence for a link between the micro-organisms that live in our intestines and the development of Parkinson’s disease. We see, for example, that people initially respond very well to the drug L-DOPA, but that the effect quickly diminishes. This may be because bacteria in the intestine that can break down L-DOPA are increasing in number. This reduces the effectiveness of the drug.’
Verbeek and his team are on the trail of a similar process, but based on an enzyme that the human body makes itself. ‘That enzyme also breaks down L-DOPA. The amount of that enzyme goes up when patients receive L-DOPA. We measure the levels of that enzyme in a clinical study. If it is high, it is better to try another drug than L-DOPA. This research is therefore very relevant for the treatment. I really like that about my job: I get inspiration for research from clinical questions, and we immediately apply the results of that research in clinical diagnostics.’
Career
Verbeek (Brielle, 1964) studied Chemical Engineering in Delft. After a year and a half of biomedical research at TNO in Leiden, he started a PhD research at the Department of Pathology at Radboud university medical center. He was visiting scholar at the University of California, Irvine CA, USA. He graduated how praise on his thesis entitled ‘Inflammatory mechanisms and pericyte involvement in Alzheimer’s disease’. After several years as a postdoc, he transferred to the Department of Neurology in 1999.
During his career, Verbeek received many grants, including Vidi, NIH and ZonMW several times, also as consortium leader. He is also a member of the scientific advisory boards of Alzheimer Nederland, Hersenstichting, Dutch CAA Association and AADC Research Trust. The appointment is effective December 1, 2022, for a period of five years.