Understanding neuroinflammation in Down syndrome dementia

Lead Investigator: Dr Frances Wiseman

• Institution: University College London
• Grant type: PhD Studentship
• Duration: 3 years
• Amount: £91,000

Why did we fund this research?

Comments from our Research Network volunteers:

I think this is an interesting and important area of work and it clearly builds on previous research.

Project summary

The team will investigate which genes on chromosome 21, which people with Down syndrome (DS) have an extra copy of, are responsible for differences in the brain using mouse models of Alzheimer’s disease.

The background

Down Syndrome (DS) affects 1 in 1000 new-borns in the UK and occurs in people who have an extra copy of chromosome 21. Sadly people with DS are at a greatly increased risk of developing Alzheimer’s Disease.

In recent years because of medical advances, the life expectancy of people who have DS has increased dramatically and on average people who have the syndrome now live to be over sixty years of age.

However, by the age of forty people who have DS have both plaques and tangles within their brains, the key hallmarks of dementia. By the age of sixty about two-thirds will have developed dementia.

What does this project involve?

Amyloid protein has been shown to build up in the brains of people with Alzheimer’s disease causing damage to brain cells. The gene that encodes for amyloid precursor protein is carried on chromosome 21.

Three copies of this gene cause early-onset Alzheimer’s disease. Other genes carried by chromosome 21, when present in 3 copies, may also play a role. 

This team believe that neuroinflammation in Alzheimer’s disease in Down Syndrome may differ from Alzheimer’s disease.

They will study different regions of chromosome 21 and investigate which genes alter neuroinflammation when three copies are present.

Next the team will use mouse models to understand the mechanisms involved. They will also study post-mortem brain tissue to see these changes in Alzheimer’s disease Down Syndrome and compare this to cases of early onset Alzheimer’s disease.

How will this project help people with dementia?

The team are hoping to find new drug targets for treatment of Alzheimer’s disease for all people, as studying this form of the disease can provide insight about how Alzheimer’s disease develops. 

By understanding which genes on chromosome 21 cause these differences in brain inflammation, we can find new ways to treat disease both for people who have Down Syndrome and also those who do not.