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When the body’s immune system is activated – by anything from bacteria to toxic chemicals – it releases certain cells that trigger inflammation. This is the cause of the swelling, redness and pain that appear when you damage your skin. A similar process called neuroinflammation occurs beneath the skin when something threatens to damage the brain. There is a growing collection of evidence that neuroinflammation may play an important role in the progression of dementia.

A colourful graphic of the brain with glowing lights around it.

Background science 

The purpose of inflammation is to defend and heal the body from damage due to injury or infection, but sometimes the immune response can persist when it is no longer needed – referred to as chronic inflammation.

Neuroimmunology is the term describing the relationship between the central nervous system and the immune system. Neuroinflammation is spearheaded by supportive brain cells called microglia. Microglia respond to damaged brain cells and foreign infectious cells by engulfing and digesting them. When microglia are responding in this way, they are described as ‘reactive’ and release inflammatory molecules.

This in turn causes a whole cascade of effects, including activating another type of supportive brain cell called astrocytes. You can read more about the different types of brain cell and how they interact with each other in this blog post. Ordinarily, astrocytes support neurones by providing them with the things they need to survive and removing their waste products. However, once activated by microglia, astrocytes become reactive and stop helping neurons survive and start destroying them.

The fluid surrounding the spinal cords of people with dementia has been found to contain higher levels of neuroinflammatory molecules than that of healthy people. In fact, neuroinflammation has now been implicated in several neurodegenerative diseases including Huntington’s disease, multiple sclerosis, and Parkinson’s disease. The range of conditions affected by neuroinflammation – not to mention the vast array of auto-immune conditions – means lots of research is under way to attempt to stop it causing damage to the brain.

 

Research

Neuroinflammation has been known to be involved in dementia for a while now but has recently seen increased attention as the dementia research landscape broadens out from targeting abnormal amyloid proteins. You can read more about amyloid and other proteins in this blog post.

A paper by a research team from Imperial College London found that reactive astrocytes may help protect neurones early in the dementia process, before becoming toxic to them as it progresses. This is an example of neuroinflammation acting as a defence mechanism against disease at first, then becoming chronic and causing destruction.

The Neuroimmunology theme within DPUK’s Experimental Medicine Incubator is dedicated to exploring the role of the immune system and neuroinflammation in various forms of dementia. A research team including Professor John O’Brien – who leads DPUK’s Neuroimmunology theme – found that neuroinflammation underpins the harmful protein build-up in three separate subtypes of frontotemporal dementia (FTD). You can read more about FTD in this blog post. Also within DPUK’s Neuroimmunology theme, Professor Valentina Escott-Price from Cardiff University is leading an ongoing project identifying and investigating genes that are related to neuroimmunology.

Equally exciting is a clinical trial that is under way to test the effectiveness of XPro1595, a protein designed to reduce neuroinflammation. After reporting significant reductions in patients’ neuroinflammation after just three months, the researchers are now extending the study for a further nine months and planning a larger follow-up study. Neuroinflammation, therefore, offers an exciting new therapeutic target that will hopefully one day generate an effective treatment for dementia.