utilities

The inflamed brain

Dr Laura PhippsKirsty MaraisClaire LucasRobin BrisbourneKaty StubbsEd PinchesGlyn Morris

This afternoon we heard about the role of inflammation in Alzheimer’s disease. Inflammation is the body’s defence mechanism; it responds to damage and infection to keep us healthy. When toxic proteins build-up in people with Alzheimer’s and other forms of dementia, the brain fights back and launches an inflammatory response to keep the damage at bay. However, while inflammation can protect the body, too much of a good thing can have its consequences. Back in 2012, research funded by Alzheimer’s Research UK revealed that a mutation in a gene called TREM2 could increase the risk of Alzheimer’s. As the TREM2 gene makes a protein heavily involved in regulating the brain’s inflammatory response, scientists suggested that inflammation might in fact play a role in the very initial stages of Alzheimer’s. The race is now on to understand the biological chain of events triggered by TREM2 mutations and how these lead to damage in the brain.

Dr Rita Louro Guerreiro was one of the team who first identified the TREM2 mutation. She presented her work on uncovering the rare mutation which leads to increased risk of Alzheimer’s. Dr Guerreiro emphasised the importance of understanding inflammation as it could provide not only a target for treatmentas a recent trial of an arthritis drug has suggested – but for diagnosis. She highlighted the need to fully understand the contribution of the immune system to the development and progression of Alzheimer’s, and it’s clear that her genetic studies have opened the floodgates for a raft of biological research.

TREM2 mutations aren’t only found in Alzheimer’s. We heard from researchers exploring the role of TREM2 in frontotemporal dementia and how mutations in the gene alter the function of the TREM2 protein. They found that some mutations prevent immune cells from carrying out an important function – eating up debris and damaging proteins. The research team believe that this could have consequences in the initial stages of FTD, and indeed other forms of neurodegeneration, when immune cells are needed to mop up the build-up of toxic proteins. They hope that altering this abnormal TREM2 function might provide a way to treat the disease.

But it’s not all about the brain. Prof Tony Wyss-Coray caused a sensation last year with his ‘new for old’ blood study in mice. In a study dubbed ‘vampirerish’ by the UK press, he found that infusing old mice with blood from young mice helped ‘rejuvenate’ the brain, improving spatial memory and boosting nerve cell communication.  This afternoon he shared his work in mice looking at how the body’s immune system changes with age and how that alters brain health. He found that when young mice were given blood from old mice, brain inflammation increased and nerve cells were damaged. Prof Wyss-Coray wants to drill down to the immune system proteins that act as messengers between the rest of the body and the brain and tease apart how they alter the brain environment – for better or for worse. Through this he hopes to understand more about the link between ageing and nerve cell death, and what can be done to prevent it.

Our brains need a high level of protection from damage and infection but it’s clear that inflammation isn’t always the ‘good guy’. Hopefully we’ll find clues about how to treat Alzheimer’s and other causes of dementia by better understanding the body’s own defence system.

You can learn more about research we fund into inflammation on the projects pages.

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