Leveraging How the Brain’s Immune Cells Fuel Frontotemporal Dementia

To elucidate how the C9orf72 gene mutation alters the brain’s immune cells to drive frontotemporal dementia by studying patient-derived cells in mice using advanced single-cell analysis.

A mutation in the C9orf72 gene is the leading genetic cause of FTD and ALS, but its role in brain cell damage remains unclear. The gene is highly active in microglia, the brain’s immune cells, which may malfunction due to this mutation. Since unhealthy microglia can worsen brain diseases, this study will explore how the C9orf72 mutation affects them. Using an innovative model that mimics a brain-like environment, I will analyze how the mutation alters microglial activity and function. This research could reveal novel drug targets and diagnostics tools.

In recent years, it has become clear that C9orf72 plays a crucial role in microglial cells, the brain’s resident immune cells — yet its specific impact on microglia remains largely unexplored. Adding to this challenge, existing in vitro systems struggle to capture microglial diversity and their dynamic responses to disease. In my project, we use an innovative model that allows me to study human microglia in a brain-like environment, enabling me to investigate how these cells respond to disease and shape its progression within the brain milieu.

Once complete, this study will provide important insights into how C9orf72 mutations affect microglial function and contribute to disease mechanisms in frontotemporal dementia. These findings will advance our understanding of microglial roles in neurodegeneration and help identify novel molecular pathways. This knowledge can inform future research aimed at developing improved diagnostic and therapeutic strategies.