January 20, 2021

expert reaction to study looking at cognitive decline in mice and a drug that reduces inflammation and boosts metabolism of macrophages

A study published in Nature looks at cognitive decline in mice when treated with a drug that reduces inflammation and boosts the metabolism of immune cells called macrophages.

Dr Susan Kohlhaas, Director of Research at Alzheimer’s Research UK, said:

“This new, well-conducted study adds to existing research implicating the immune system in the development of age-related cognitive decline.  These findings highlight a molecular pathway that could potentially be targeted to restore healthy immune system activity in both the body and the brain.

“This study looked at mice with immune system changes similar to those that we see during human ageing, which may be relevant to Alzheimer’s and other types of dementia.  The authors showed that targeting a molecule that’s expressed on a certain cell type in mice could reduce inflammation in the brain and may improve the function of the hippocampus, an area of the brain important for memory.  Disrupted immune system activity in the brain is thought to be an important aspect of the complex biology of Alzheimer’s disease, but there are many other processes at play as well.

“While intriguing, this is early-stage research carried out in mice and while the results deserve further follow up, there are many steps to go before we will know if this is likely to be a successful strategy for treatment of dementia.  To understand more about how restoring the activity of immune cells in the brain affects the brain health and ultimately memory and thinking skills in humans, we need to see experiments in environments that closely mirror the human brain.

“The brain is a complex network of cells connecting together to form your thoughts, memories and personality.  Finding ways to maintain brain health as we age and protect it from diseases like Alzheimer’s is perhaps our greatest long-term medical challenge and it is essential that we fund research to follow up important work like this.”

Prof Jennifer Pocock, Senior Lecturer, Institute of Neurology, UCL, said:

“This is interesting and certainly supports a role for PGE2- EP2 signalling in ageing and for a role in inflammatory cell metabolism, although it is unlikely to be the only signalling pathway involved in macrophage or microglial metabolism and may affect a wide range of cells than those reported.  This would need careful consideration.”

Prof Tara Spires-Jones, UK Dementia Research Institute at The University of Edinburgh & Deputy Director, Centre for Discovery Brain Sciences, University of Edinburgh, said:

“This study from Dr Andreasson and colleagues at Stanford shows that restoring the function of immune cells called macrophages can improve memory in aged mice.  This study is important because it shows that in mice, age-related memory decline can be reversed; however, it is important to note that this research was in small groups of mice and more work will need to be done to determine whether the same effects will be possible in people.”

‘Restoring metabolism of myeloid cells reverses cognitive decline in ageing’ by Paras S. Minhas et al. was published in Nature at 16:00 UK time on Wednesday 20 January 2021.

DOI: 10.1038/s41586-020-03160-0

Declared interests

Dr Susan Kohlhaas: “No interests to declare.”

Prof Jennifer Pocock: “No conflicts of interest.  I work on the role of microglia in Alzheimer’s disease and we have published papers on the role of metabolism in these cells in AD.”

Prof Tara Spires-Jones: “I have no conflicts of interest with this study.”