What role does the immune system play in recognising the Alzheimer's disease hallmark, amyloid?

Lead Investigator: Dr Martha Triantafilou
Institution: Cardiff University
Grant type: PhD studentship
Duration: 3 years
Amount: £74,785
Scientific Title: The role of pattern recognition receptors in amyloid-beta-induced inflammation

What do we already know?

Plaques, or clumps, of a protein called amyloid are one of the hallmarks of Alzheimer's disease. It is thought that inflammation surrounding these plaques plays a large role in the development of Alzheimer's disease.

Inflammation in this case doesn't refer to the swelling that is seen in some areas of the body following an injury, but to chemical changes that are used to fight infection or changes within the brain. It is thought that this inflammation may change conditions within the brain, and a large amount of inflammation may trigger the build-up of proteins associated with the development of Alzheimer's disease.

Although we know that the immune system is responsible for triggering this inflammation, how this happens is not completely understood. The immune system has been primarily viewed as a first line of defence to "danger" for the brain. It is rapidly activated and eliminates the danger with an inflammatory response.

In order to sense the intruders, the immune system has what are called 'pattern recognition receptors' (PRRs). These identify things that shouldn't be there and mount an inflammatory response.

There are many different kinds of PRRs. It was originally thought that these different types of receptor acted individually. However, evidence suggests that there is co-operation between these receptors in order to trigger the inflammatory response. Simultaneous detection of intruders or danger by distinct PRR types confirms the presence of genuine danger, justifying the inflammatory response.

Different types of PPRs have been found within amyloid plaques. How different types of PRR interact with each other during Alzheimer's disease to produce this reaction has not been studied before.

What does this project involve?

This project will investigate whether the build-up of amyloid in the brain can cause the inflammatory process, and through this cause the problems that can lead to damage and the symptoms of Alzheimer's disease.

The researchers will look at the different receptors that make up the immune system within the brain, and investigate how they interact and work together to recognise amyloid deposits. They will look at precisely which kind of receptors are involved in the inflammation surrounding amyloid, and investigate how this can lead to the processes that cause Alzheimer's disease.

This project will also try to understand the role of the immune system in normal clearance of amyloid, and what changes to result in amyloid plaques.

How will this benefit people with dementia?

This project will provide a greater understanding of the process surround inflammation in the brain that is associated with Alzheimer's disease. This will help us to further understand how the immune system responds to amyloid, and how it may play a role in amyloid clearance, in a healthy brain. This will show the changes the occur to allow build-up of amyloid to form plaques, and the surrounding inflammation that contributes to the symptoms of Alzheimer's disease.

Understanding the role that different types of receptors within the immune system play, and how these interact with each other, could provide targets for future treatments to prevent the changes that lead to Alzheimer's disease from happening.