Investigating how mutations affect brain inflammation in frontotemporal dementia

Frontotemporal dementia (FTD) is a relatively rare form of dementia which usually affects people under 65, often causing personality and behavioural changes.

A hallmark of various forms of dementia, including FTD, is the build up of a protein called TDP-43. Some people with FTD also have mutations in the TDP-43 gene. Scientists have discovered that these mutations increase inflammation in the brains of mice with features of FTD.

Inflammation in the brain is thought to rapidly accelerate the progression of dementia. Understanding its underlying cause may pave the way to new treatments.

To understand how mutations in TDP-43 can cause brain inflammation, researchers from King’s College London are transforming human stem cells into microglia, a specific type of brain cell important for regulating inflammation.

Dr Ghosh willstudy the effects of TDP-43 mutations on the ability of microglia to function and regulate brain inflammation.

Initial experiments from the group have found that TDP-43 mutations cause microglia to become overactive, which may eventually lead to the loss of nerve cells.

This funding  will allow Dr Ghosh to confirm these findings in mice with TDP-43 mutation, and features of FTD.

The overall aim of the project is to increase the understanding of how TDP-43 causes brain inflammation, and ultimately to help identify new treatment approaches for dementia.