Investigating the effect of insulin on brain cells in Alzheimer’s disease

Lead Investigator: Dr Claire Garwood

Institution: University of Sheffield 

Grant type: Junior Fellowship

Duration: 36 months

Amount: £204,615

Scientific Title: Consequences of impaired insulin signalling in astrocytes: A role in Alzheimer's disease 

Why did we fund this project?

Comments from members of our Research Network:

'I think this line of research could produce useful information in the not too distant future. Use of human derived cells and the 3D growing system are particularly commendable'

'An interesting and well-presented application ... Good dissemination plans building on current Alzheimer's Society links'

'Clearly the research team has great expertise and the application of a 3D growing system to model how cells operate in the brain sounds an exceptionally interesting approach'

What do we already know?

Type-2 diabetes has been shown to increase the risk of developing Alzheimer's disease. Diabetes is caused by problems with the way that the body produces or uses the hormone insulin. Recent research indicates that there are similar problems with the way that insulin works in the brains of people with Alzheimer's disease. 

This project is particularly focusing on the effect that insulin has on specialised brain cells called astrocytes. Astrocytes maintain the brain environment, supply nerve cells with essential nutrients and restore brain functioning after an injury.

The two hallmark Alzheimer's disease proteins, amyloid and tau, are deposited in and around nerve cells in sticky clumps, causing damage to the cells. However, the involvement of these protein clumps in disease development is not clear.

Dr Garwood and her colleagues have previously shown that, as the levels of amyloid and tau clumps increase in the brain, astrocytes lose their ability to utilise insulin. This may affect their function and could also stop the neighbouring nerve cells from working properly.

What does this project involve?

Dr Garwood believes that disrupted insulin signalling can alter astrocyte function and also have a detrimental effect on the nerve cells that they support. She also believes that disrupted insulin signalling will prevent astrocytes from coping with the clumps of amyloid protein.

The project will investigate this using cells in the lab that are derived from human nerve cells. She will use various techniques to determine how insulin affects these cells, and the effect that the amyloid protein can have on this process. This includes investigating whether the presence of amyloid clumps can prevent astrocytes from communicating with other cells in the brain, leading to these other cells not being able to function correctly. 

One aim of this study is to refine a method that will grow cells in a three-dimensional environment. This innovative method will allow the researchers to examine lab-grown cells in a way that more closely represents the environment seen in the brain. 

How will this benefit people with dementia?

 Understanding how impairments in insulin signalling cause the brain to be more susceptible to disease will allow us to better understand the factors that are involved in the very earliest stages of Alzheimer's disease. This is key for designing better treatments and may help us to discover ways to prevent dementia development. It will also enable researchers to determine why some people are more at risk of developing the disease than others, and to find ways to help those who are most affected.