Understanding the effects of the diabetes type 2 drug Metformin on models of Alzheimer’s disease

Lead Investigator: Dr Teresa Niccoli

• Institution: University College London
• Grant type: PhD studentship
• Duration: 36 months
• Amount: £90,762

Project summary

Metformin is a common diabetes type 2 medication, which has been shown by previous research to have both good and bad effects when used as a potential treatment for Alzheimer’s disease.

This research will try to understand the parts of a brain cell metformin targets to have a beneficial effect which could help design future Alzheimer’s disease treatments for the future. 

The background

Metformin is an existing treatment for people living with type 2 diabetes and is one of the most prescribed drugs in the world.

Diabetes is a risk factor for dementia and is associated with increasing a person’s risk of developing dementia later on in life. Although there is increasing evidence that Alzheimer’s disease might be linked to problems with the body’s metabolism (the chemical reactions in the body that provide our cells with energy), how diabetes increases the risk of developing dementia is still not well understood. 

Metformin has shown promise as a potential Alzheimer’s disease therapy in a small-scale clinical trial. Dr Niccoli and team have also conducted previous studies in fruit fly models of Alzheimer’s disease treated with Metformin which have also shown an improvement in symptoms.

However, Metformin treatment has also been shown to increase the build-up of amyloid protein (a hallmark of Alzheimer’s disease) in the brain, which is an unwanted negative effect. Therefore there is a real need to understand in more detail how Metformin interacts with the Alzheimer’s disease brain.

What does this project involve? 

This project looks to try and further understand the ‘good’ and ‘bad’ effects of Metformin on Alzheimer’s disease. The researchers hope to find out how Metformin improves Alzheimer’s disease symptoms and also what causes it to increase the unwanted amyloid plaques.

They will use fly models of Alzheimer’s disease to identify any genes that are affected by Metformin treatment which also reduce the toxicity of amyloid protein build ups. They will then try to work out how these genes have this effect.

Finally, they will then look at these genes in human brain cells grown in a dish that are affected by Alzheimer’s disease. This will help the researchers understand metformin’s previously described beneficial effects. 

How will this project help people with dementia? 

There is currently no treatment for any type of dementia that stops or slows down the progression of disease.

To develop effective treatments, understanding exactly which parts of a brain cell to target with drugs is essential.

By untangling the “good” and the “bad” effects of metformin, researchers will know which parts of a human brain cell metformin targets to have a beneficial effect.

This knowledge could give the dementia research community another part of the brain cell to target with future treatments, which could be used to develop future Alzheimer’s disease drugs that might slow down progression of the disease.

These treatments would be more targeted and would avoid the previously described unwanted side effects of metformin treatment.