A major aim in this research theme is to understand how aberrantly adapted synaptic and circuitry function contributes to neurodegenerative diseases, such as Alzheimer’s disease (AD) and frontotemporal disorders (FTD). To investigate this, we integrate molecular, cellular and behavioural approaches and try to reach a systems level understanding of neurodegenerative disorders.

• Interventions using opto- and chemogenetic approaches (Ronald van Kesteren, Michel van den Oever) are important to obtain causal understanding of mechanisms that are affected at the cellular and circuitry level and how this contributes to cognitive impairment.

• The effect of tau pathology on the formation, stability and reactivation of memory engrams is studied by Michel van den Oever and Priyanka Rao-Ruiz.

• Mark Verheijen investigates how glial cells influence the development of pathology and cognitive decline in mouse models of AD.

• We also use high cellular models  and high-throughput cellular assays (e.g. cellomics). Recently, the use of iPSC-derived human neurons was introduced as these may represent cellular dysfunction in the specific genomic context of the patient.

• Postmortem human brain tissue of AD and FTD cases is used in proteomic analyses to dissect molecular adaptations in the human brain (Guus Smit, Ronald van Kesteren).