Understanding how the immune system contributes to Alzheimer’s disease development

Research project: Role of redox sensing ITAMs in directing the inflammatory response to Alzheimer’s Disease synapses

Lead Researcher: Professor Will Wood

Institution: University of Bristol

Grant type: Project

Amount: £200,168

Duration: 36 months

Why did we fund this project?

Comments from members of our Research Network:

'This project is presented very clearly and it could be helpful to be able to detect dementia as early as possible, particularly if effective treatments can also be developed.'

'This work really is at the front-edge of finding out why and how AD develops. The use of time-lapse video microscopy sounds very exciting to actually see the inflammatory response.'

'A well thought out and presented application which makes clear the work to be undertaken. The outcome hopefully will lead to a better understanding of how dementia progresses in the brain.'

What do we already know?

There is an increasing amount of evidence that the underlying mechanisms behind Alzheimer's disease may begin years or even decades before symptoms start to show. Many researchers believe that treating those affected at the earliest stage possible will be the most effective way of slowing down the disease or stopping its progression.

The brain's immune system has long been implicated as a key factor in the development of Alzheimer’s disease, particularly a specialised type of immune cell called microglia. The microglia help to clear debris and toxic materials from the brain. However, it appears that in Alzheimer's they do not perform this function correctly or may even contribute directly to the disease process.  One theory is that the Alzheimer’s hallmark amyloid protein activates the microglia, which perform their function properly at first but as more amyloid is produced the system becomes overwhelmed and unregulated. This leads to damage to brain cells.

Some trials for potential Alzheimer's disease treatments have attempted to prevent the damaging immune response but so far results have been disappointing. This could be because the drugs are broadly targeting the whole immune system rather than just the faulty microglia.

What does this project involve?

The researchers on this project are hoping to understand more about the role of the immune system in Alzheimer's disease to find out if there is a way to target the microglia more effectively with treatments. The team have previously used cutting-edge imaging techniques in fruit flies that have shown that immune cells will travel to areas of the brain where the amyloid protein is present. It is thought that the microglia travel to the amyloid in order to remove it from the brain, but if they become overactive they may end up damaging the brain cell in the process. The researchers will therefore use this imaging technique to understand how the cells travel during the disease process and what the relationship is between the microglia and the amyloid protein. They will then unpick the genetic and molecular aspects that control this behaviour.

How will this benefit people affected by dementia?

It is clear that the immune system plays a role during the development of Alzheimer’s disease. Understanding what this role is will lead researchers to better understand how to more accurately target this system in order to try and prevent a key early-stage disease process.