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Research

Changing minds about Alzheimer's

Protecting against memory and behaviour changes

Published: 11 September 2018

Approximately 46 million people worldwide are living with dementia, and every three seconds someone is diagnosed with the condition. Researchers at Southampton have shown that regulating immune cells in the brain could prevent the memory loss and behaviour changes seen in the progression of Alzheimer’s – a finding that could have a huge impact on future research into the disease.

New thinking

Along with his team, Dr Diego Gomez-Nicola, lecturer and research fellow within Biological Sciences at the University, is currently studying a relatively new strand of research into Alzheimer’s – the role of inflammation in the progression of the disease. This approach was pioneered by professors Hugh Perry and Clive Holmes, both working at Southampton, who showed that inflammation such as a cold or infection can worsen the disease.

“Our research focuses on cells called microglia: the immune cells of the brain. When too many of these cells are produced, inflammation is caused in the brain and therefore the disease is accelerated.”

The work, funded by the Medical Research Council (MRC) and Alzheimer’s Research UK, compared tissue samples from healthy brains to those with Alzheimer’s. After counting the number of microglia in both samples, the team found that they were more numerous in the brains with Alzheimer’s. In addition, the activity of the molecules regulating the numbers of microglia correlated with the severity of the disease.”

Scientists in Southampton have been at the forefront of research into the role of the immune system in Alzheimer’s.

Dr Diego Gomez-Nicola - Lecturer and Research Fellow

Improve cognitive skills

“We then studied the microglia in a mouse model, which has been bred to have aspects of Alzheimer’s. We wanted to find out whether blocking the receptor responsible for regulating microglia, known as CSF1R, could improve cognitive skills,” explains Diego.

The team gave the mice oral doses of an inhibitor that blocks CSF1R and found that it could prevent the rise in microglia numbers seen in untreated mice as the disease progressed. In addition, the inhibitor prevented the loss of communication points between the nerve cells in the brain associated with Alzheimer’s, and the treated mice demonstrated fewer memory and behavioural problems.

“Importantly, we found the healthy number of microglia needed to maintain normal immune function in the brain was preserved, suggesting the blocking of CSF1R only reduces excess microglia,” says Diego.

“In the last few years, scientists in Southampton have been at the forefront of research into the role of the immune system in Alzheimer’s, so it is encouraging to see this study taking these ideas forward by identifying a specific mechanism that could be a target for future treatments,” said Dr Simon Ridley, Director of Research at Alzheimer’s Research UK.

 

Collaborating for success

The next step is to use the findings to improve the lives of people with Alzheimer’s disease. Diego and his team are part of the Dementia Consortium, a collaboration between Alzheimer’s Research UK, MRC Technology and pharmaceutical companies Eisai, Lilly and AbbVie. “Our role is to design and test better inhibitors for CSF1R with the aim of developing better drugs with a profile that more specifically targets the brain,” says Diego.

The team is also part of the Wellcome Trust Immunology Consortium. “We liaise with industrial partners such as GSK, Pfizer, Lundbeck and Johnson & Johnson to investigate whether commercially available drugs, which are licenced for other diseases, could be used to target brain inflammation and therefore be repurposed for use against Alzheimer’s,” explains Diego.

Diego hopes that in five years’ time progress from these two initiatives could mean the research is closer to clinical trials, and closer to confirming the impact of microglia on cognitive output.

Find out more about Dr Diego's research

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