In getting older, we do not always only get more wisdom, but sometimes other things can come up, such as mild cognitive impairment (MCI). This is often one of the first clinical signs that there will be a chance of Alzheimers disease (AD) and frontotemporal dementia (FTD). In these dementia subtypes, there are some proteins that are characteristic for these diseases. In AD for example, those proteins are the beta amyloid (Aβ) protein fragments, and are located outside of the braincells, while tau proteins are also present, but are located inside the braincells. In FTD, tau proteins are more abundant compared to Aβ proteins. Although there is a difference in the type of protein, in both subtypes there is breakdown of these brain cells occurring, which indicates that the underlying cell mechanisms may be very silimar. The breakdown of brain cells isn't limited to neurons, which are the biggest and best known brain cell type, but also astrocytes, oligodendrocytes, and glial cells. These three cell types are crucial in supporting and maintaining proper functioning of the neurons, and altogether, they form a powerful functional network. As they are working closely working together, any positive or negative effect on one of the cell types will influence how the other cells will function.
In this Pillar, we will attempt to make cell models of this; we will use human donor cells, usually derived from the upper layer of the skin, which we can reprogram to become so-called induced pluripotent stem cells (iPSCs). These cells will be able to develop and grow into "tiny organs'" or in this case "tiny brains". We call the latter brain organoids. This way, we can use a very non-invasive method to study cellular mechanisms and molecular processes in human cells, and study how the cell types interact with each other. The more we get to know about what happens and how, the better we can explore which therapeutic targets may arise that will hold potential for future treatments or interventions.
Image 1: an overview of the different projects (1-6) that will be executed in Neuron-Glia. In the middle, the different interactions between neurons and glia are displayed: 1) tau pathology & neuron-glia stress signaling; 2) reactive astrocytes & neural function; 3) microglia interactome; 4) aging-related transcription stress; 5) molecular profiling of patient-derived cultured cells; 6) cholesterol metabolism. Source: Vrije Universiteit Amsterdam
In this Pillar, prof. Elly Hol (UMC Utrecht), dr. Wiep Scheper (Amsterdam UMC/VU), prof. Bart Eggen (UMC Groningen), dr. Rik van der Kant (VU), dr. Williane Vonk (Prinses Máxima Centrum), and prof. Daniel van den Hove (Maastricht UMC) are involved. They will supervise PhD-students, postdocs, and other (non-)scientific staff.
Read more about the people involved here, about who they are, and what they do.