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A game of Mastermind to unravel Alzheimer’s disease

In order to better understand the course of Alzheimer’s disease, Frédérique Kok believes that a strategic and structured approach is needed: the Mastermind research approach. With her LUF grant, Kok wants to generate high-quality data to build a mathematical model that can recognize the onset of the disease and predict its course.

Crack the code

‘As a consequence of the ageing population, Alzheimer's disease is becoming more and more common,' says Kok. However, there is no cure yet and we can often only diagnose it when it is already too late.' However, long before symptoms such as dementia appear, processes that lead to the responsible brain damage are already in progress. 'When we gain more insight into this early phase of the disease, it offers opportunities for early diagnosis and thereby to delay or even halt the disease'.

Kok wants to obtain this insight by using the 'Mastermind method'. Her group leader professor Liesbeth de Lange of the Leiden Academic Centre for Drug Research devised this approach. 'In the game of Mastermind, you have to work strategically and in a structured way to crack the code,' explains Kok. ‘That is exactly what I would like to do with Alzheimer's disease. Using animal models, Kok will collect as much data as possible about which biological compounds are present in different parts of the body during the development of the disease over time. A mathematical model can then search for relations between the compounds present and the stage of Alzheimer's disease in which a patient finds himself. 'My hope is that such a model enables us to diagnose people before they develop symptoms.'

Trends and relations

For the pilot study, Kok will measure no less than 23 cytokines in the brain, spinal fluid and blood. 'Cytokines are inflammatory proteins that play an important role in brain inflammation. These inflammatory factors seem to play a key role in the development of Alzheimer's.' Later, Kok and her colleagues from the Predictive Pharmacology research group will combine the data on cytokines with comparable data on other substances, such as other proteins and fats. 'It is important that the study is longitudinal, which means that the measurements in each individual are repeated at a number of consecutive times. In this way we can really study the course of the disease,' says Kok. 'We hope to find trends, but also relationships between the different body compartments. I am also very curious about the possible differences in trends between the 23 types of cytokines that we are going to measure'.

Individual pieces or the complete picture

'I like this research because of its great social relevance: everyone knows someone who has been affected by Alzheimer's or dementia,' says Kok. 'My passion is to unravel the molecular mechanisms of diseases. In this way, I hope to contribute to the possible development of medicines.' Although Kok is already a fan of the Mastermind method, its use is not yet widespread. 'The duration of research projects is often too short and people look too much at the individual pieces. That way you don't solve complex diseases such as cancer or Alzheimer's, because you lack insight into the interrelationships between the different factors that together cause a disease as a whole.' Kok's structured measurements and the mathematical model can hopefully bring about change. 'Receiving this grant means a lot to me.  Thanks to the LUF, the first step can now be taken. I hope that this will lead to new successes, both in terms of research results and subsequent grants.'

Cover photo: Frédérique Kok (left) with group leader Liesbeth de Lange


The aim of the Leiden University Fund (LUF) is to help Leiden University to thrive. One of the ways the LUF achieves this aim is by awarding grants to Leiden University scholars and students.

Kok receives a LUF project grant of €25,000 from the Den Dulk-Moermans Fund, which funds research into all aspects of health.

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