Dementia Discovery Group

The research in our group focusses on understanding the early cell biological processes that drive Alzheimer’s Disease and other related dementias. We use human stem cell-derived neurons, astrocytes and microglia combined with CRISPR-Cas9 gene-editing to understand how genetic factors drive the earliest stages of disease pathogenesis. We use this knowledge to develop novel drugs for these disorders, with a strong focus on lipid metabolism.

In a healthy brain neurons, astrocytes and microglia closely work together by the exchange of molecules and proteins. Neurons are the cells responsible for transmitting information, microglia are the immune cells of the brain and astrocytes  are the homeostatic regulators. In late stages of Alzheimer’s disease and related dementias, neurons eventually die and cause memory problems. However, the cause for this death remains unknown. Over the last years, it has become increasingly clear that problems in the Alzheimer’s brain start with changes in microglia and astrocytes. In addition to the well known Amyloid and Tau pathology, glial lipid accumulation is a major pathology of Alzheimer’s. In fact, Alois Alzheimer had already described lipid saccules as a characteristic of the Alzheimer’s Disease in 1907.  Over recent years, our work and the work of our colleagues, has refocused the attention of the field towards lipids as one of the early drivers of Alzheimer’s disease. In our lab we aim to 1) understand how changes in lipid metabolism may drive Alzheimer’s disease and related dementias and 2) develop lipid-targeting interventions to treat these brain disorders.

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