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

Research project: The role of pattern recognition receptors in amyloid-beta-induced inflammation

Lead Investigator: Dr Martha Triantafilou
Institution: Cardiff University
Grant type: PhD studentship
Grant amount: £74,785
Start date: October 2012
Completion date: March 2016

What was the project, and what did the researchers do?

Toxic clumps of amyloid protein found in the brain are one of the hallmarks of Alzheimer's disease. It is thought that inflammation surrounding these clumps, caused by the immune system, 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 in the brain.

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 these receptors. It was originally thought that these acted individually, however evidence suggests that there is co-operation between these receptors in order to trigger the inflammatory response. Simultaneous detection of intruders such as an infection by distinct receptor types confirms that the danger is real, therefore justifying an inflammatory response.

The researchers wanted to identify the different receptors that are involved in recognising amyloid beta and how they might be cooperating with the immune system to trigger the inflammatory response. The researchers used human brain cells and looked at the response of these cells to the amyloid beta protein and a soup of immune boosting proteins found in blood and tissue fluids. 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.

What were the key results, and how will this help in the fight against dementia?

In this study the researchers were able to establish which pattern recognition receptors were recognising amyloid in a specific type of brain cell, called astrocytes. Astrocytes provide structure in the brain and protect the neurons while they are sending vital signals, among other functions. The researchers determined that the receptors that were responding to amyloid were communicating with a part of the immune system known to initiate production of some inflammatory proteins. This was responsible for creating the increased inflammatory response. 

The researchers in this study were able to use a combination of drugs to block the complicated interactions between the cells and the immune system to reduce the levels of inflammation produced in response to amyloid beta. The information gained from this study could prove another step towards effective treatment to curb Alzheimer's progression.

What happened next? Future work and additional grants

Preliminary experiments into preventing the inflammation response to amyloid beta have shown great promise. The researchers plan to expand on their findings to test whether this method has the same effects in mice with features of Alzheimer's disease, with the aim of moving closer to a potential new approach for treatment.

How were people told about the results? Conferences and Publications

Conferences:

Triantafilou et al; 9th International Conference on Complement Therapeutics, July 2016, Rhodes, Greece

Alzheimer's Society annual research conferences , Manchester, June 2015

The British Society of Immunology Annual Congress, Dec. 2014, Brighton, UK

Alzheimer's Society annual research conferences, Nottingham, July 2014

Alzheimer's Society research talk event in Cardiff, November 2014

The British Society of Immunology Annual Congress, Dec. 2013, Liverpool, UK


 

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