Pillar 1: gliADiversity

Dementias like  Alzheimer’s disease (AD) and frontotemporal dementia (FTD) . are characterised by the accumulation of protein clumps that result in dysfunction and loss of nerve cells In AD, those proteins are the beta amyloid (Aβ) protein fragments, that are located outside of the brain cells, while tau proteins are also present, but are located inside the brain cells. In FTD, this can be tau or TDP43 proteins. Although there is a difference in the type of protein, in both diseases there is  breakdown of nerve cells (neurons) occurring, which indicates that the underlying cell mechanisms may be very similar. The disease process  is not limited to neurons, the cells that are performing the core brain functions in for example memorybut also astrocytes, oligodendrocytes, and microglial cells. These three cell types are crucial in supporting and maintaining proper functioning of the neurons and comprise the immune system of the brain. Together the brain cells 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 study these cell-cell interactions in  cell culture We use human donor cells, usually derived from the upper layer of the skin, which are reprogrammed to become so-called induced pluripotent stem cells (iPSCs). These cells will be able to develop and grow into different brain cells. 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

Who is involved?

In this Pillar, prof. dr. Wiep Scheper (Amsterdam UMC/VU), prof. Bart Eggen (UMC Groningen), prof. dr. Elly Hol (UMC Utrecht), dr. Rik van der Kant (VU), and prof. Daniel van den Hove (Maastricht UMC) are involved. They supervise PhD-students, postdocs, and other (non-)scientific staff.

Read more about the people involved here, about who they are, and what they do.