Mechanisms Of DEMentia (MODEM): connecting the dots

30 March 2023

“We all believe in the importance of a different piece of the puzzle.” prof. dr. Guus Smit says when he explains why this consortium was formed together with 20 other researchers. “It’s about connecting the dots, the cohesion between seemingly different processes underlying the development of dementia from different perspectives. That is what we are looking for in Mechanisms Of DEMentia (MODEM). Because that coherence has to be there. There is no other way.”

Dementia is a term for several brain disorders involving memory loss and neurodegeneration, such as in Alzheimer’s disease (AD) and fronto-temporal dementia (FTD). At the time of diagnosis, the disease process has long been ongoing. But where and when does it begin? The MODEM consortium aims to find the causes of dementia, by understanding the underlying mechanisms of dementia from different perspectives.

Improve treatment by finding the cause
There are probably multiple causes of dementia, and different types of dementia in turn involve different mechanisms. This makes research very complex. Currently, we know that dementia is characterized in the brain by accumulation of proteins inside and outside brain cells, causing stress and inflammation and cell death. There are also problems with the blood vessels within the brain. Currently, there is no effective treatment for dementia; better understanding of these mechanisms can lead to improvement in diagnostics, development of therapies, and thus better treatment.

Solving a gigantic puzzle
The strength of MODEM lies in the researchers: all 20 researchers each have their own expertise, their own piece of the puzzle, but can use it to solve the puzzle together. By looking at the causes and underlying mechanisms of AD and FTD, four main lines can be distinguished:

1. The development of human models of brain cells and organoids, with a focus on interactions between different types of brain cells.
2. Next to human models, research of postmortem tissue, and animal models is being done to look at memory and pharmaceutical interventions/treatments.
3. Using advanced imaging techniques, such as MRI and PET scans, to learn more about activity of neural networks and blood flow in the brain. This line focuses on biomarkers that can be found in the blood, and thus also in the bloodstreams of the brain.
4. The last line focuses on data analysis and bioinformatics, by looking for biomarkers in certain tissues what comes from old and new data.

Connection between the lab, the clinic, and the patients
These four projects generate a lot of potential within the research field of dementia; for example, more knowledge is gained about the mechanisms of the disease itself, as well as opportunities for new treatments and therapies. Also, novel insights may emerge for better use of imaging techniques in diagnosis, as well as better identification of more specific forms of dementia. All this is supported by the search for the biomarkers using data analysis; with more and strong biomarkers, dementia can be better diagnosed.

Organization & collaboration
MODEM is part of ZonMW’s Dementia Research Program, with MODEM fulfilling the Fundamental Research work package. MODEM is a national consortium, led by Prof. Dr. Guus Smit (VU Amsterdam). Also involved in the consortium are Amsterdam UMC, Leiden UMC, UMC Utrecht, UMC Groningen, Radboud UMC, Erasmus MC, University of Amsterdam, Maastricht UMC and Prinses Máxima Centrum.

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Foto: kick-off meeting MODEM, VU Amsterdam (maart 2023)