Investigating how changes to the immune system could be linked to development of Alzheimer’s disease

Research project: Cell Biology of Complement Receptor 1 in Alzheimer's Disease

Lead Investigator: Professor Paul Morgan
Institution: Cardiff University   
Grant type: Project Grant 
Duration: 36 months
Amount: £250,000

Why did we fund this project?

Comments from members of our Research Network:

'The proposal builds on recent, exciting discoveries.'

'As drugs directed at the complement pathway are currently available, this offers an opening for drug re-purposing to take place.'

'This research seems to me to be the start of an exciting and novel approach in understanding some of the hereditary factors involved in the development of this disease.'

What do we already know?

Our immune system responds to infection or injury by activating a number of molecular systems that can clear away anything toxic. One of these systems is called complement, which is a series of proteins that remove infections or toxic debris from the body. In the brain, complement works by recruiting specialised immune cells called microglia, which 'eat' the source of the damage, clearing it away. 

Researchers increasingly believe that the immune system plays a key role in the development of Alzheimer's disease. One potential reason for this is that microglia are not clearing away the toxic proteins associated with the disease well enough, leading to damage to brain cells. 

This theory is backed up by the fact that changes to a gene called CR1 appear to be linked to an increased risk of Alzheimer's disease. CR1 is found on the surface of microglia and helps them to recognise other parts of the complement system. 

What does this project involve?

Professor Morgan and his team will work to understand more about how changes to CR1 associated with Alzheimer's disease can affect the complement pathway and microglia.

They will use cells in the lab that make the version of CR1 associated with Alzheimer's disease. They will understand how these changes affect the way CR1 functions, including how it is transported within microglia and whether the changes affect how it binds to other molecules in the complement system. 

How will this benefit people with dementia?

There is increasing evidence that the immune system plays an active role in the development of Alzheimer's disease. Understanding the molecular reasons behind this are vital to discover potential targets for the development of treatments. As there are already existing drugs that target the complement pathway, this project could be the first step in uncovering a new angle for developing treatments 
 

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