How does genetic variation affect microglia response?

Summary

Investigating how Alzheimer’s disease (AD) risk genes affect the immune cell of the brain, the microglia. This will improve our understanding of altered microglial responses in AD, and pinpoint new therapeutic targets

How are we doing it?

We are using microglial like cells differentiated from iPSCs (induced pluripotent stem cells) with specific genetic differences to allow us to study the role of ABI3 in microglia and the effect of the variant S209F.

• iPSCs will be differentiated into microglial like cells and we will gather data on gene expression and cell structure.
• Microglial function will be further compared by exposing them to activation compounds and collecting images, transcriptomic data, and proteomic data.
• Microglial lines will be integrated into organoids, a 3D cell culture model, to explore the role of ABI3 and ABI3 S209F in a more complex environment.

What happens next?

The data gathered on how AD risk genes affect microglia will contribute to understanding of microglial dysfunction in AD which could aid identification of treatment targets.

Funding

National Institute for Health and Care Research (NIHR) Exeter Biomedical Research Centre (BRC)

People Involved

Dr Thomas Piers and Professor Jonathan Mill