January 8, 2016

expert reaction to blocking brain inflammation in model of Alzheimer’s

A study published in the journal Brain has reported that blocking a receptor in the brain which is responsible for regulating immune cells could protect against the memory and behaviour changes seen in the progression of Alzheimer’s disease.

Prof. John Hardy, Professor of Neuroscience, UCL, said:

“This is a very interesting piece of work which should and will attract a wide interest.

“Neuropathologists have always said how much microglial activation occurred in Alzheimer’s disease and two years ago we showed, by genetic analysis, that those who had a defective microglial activation were more likely to get Alzheimer’s disease and that this activation followed the deposition of the amyloid protein in mouse brains.  This work suggests that modifying this response to amyloid may help therapeutically.

“A word of caution: it will be nice to see this work repeated in other models.”

Dr Mark Dallas, Lecturer in Cellular and Molecular Neuroscience, University of Reading, said:

“This is an exciting discovery which could explain why drugs designed to treat Alzheimer’s have so far been unsuccessful.

“Studies have previously detailed that cells other than the nerve cells within the brain play a vital role in the progression of Alzheimer’s disease. This study focuses on microglia cells, the so-called ‘guardians of the brain’ that protect the brain from infection.

“By targeting a cell-specific receptor, the researchers show the ability to prevent memory deficits, although the characteristic amyloid plaques still build up in the brain. This is intriguing and could provide insight into why drugs disrupting amyloid plaque formation have so far failed to provide patient benefit.

“While this basic science research provides strong evidence, the challenge will now be to develop medicines for people with dementia, so we await the development of clinical treatments with interest. Too often, this has been the stumbling block in turning observations in the laboratory into a workable therapy.

“Excitingly, it does however highlight new avenues for researchers to exploit and strengthens the case for targeting other cell types within the brain in the fight against Alzheimer’s.”

Prof .Gordon Wilcock, Emeritus Professor of Geratology, University of Oxford, said:

“It is encouraging to see that blocking the  proliferation of inflammatory cells, i.e. microglia, seems beneficial in this mouse model,  as it could lead to the development of new treatment strategies for Alzheimer’s disease, and also some other neurological conditions.

“However, although this is a carefully conducted study combining data from brain samples from Alzheimer patients with data from the transgenic mouse model experiments, we will have to await the outcome of clinical trials to really know how relevant these findings are to patients with Alzheimer’s disease.”

Dr Doug Brown, Director of Research at Alzheimer’s Society, said:

“We know brain inflammation occurs in Alzheimer’s disease, but researchers are still working out what impact this has on the progression of the disease.

“This study shows that the production of new immune cells in the Alzheimer’s brain contributes to the development of memory impairments – and that by blocking this immune reaction memory loss can be reduced. It’s encouraging to see that these new findings are already being taken forward to see whether they can help in the development of new dementia treatments.

“This study extends earlier working looking at inflammatory processes in neurodegenerative conditions and provides convincing data that the production of new immune cells in the brain is involved in the development of Alzheimer’s disease. Although the researchers have only confirmed this process is involved in mice models of Alzheimer’s, they provide some evidence from post-mortem brain tissue to suggest that their findings are likely to be relevant to the disease in humans.

“With an ageing population and no new dementia drugs in over a decade, the need to find treatments that can slow or stop disease progression is greater than ever. Although dementia research is still desperately underfunded, increased commitments from government and charities are boosting UK research efforts and contributing to faster global progress towards a much needed cure.”

Professor Paul Morgan, Director of Cardiff University’s Systems Immunity University Research Institute (SIURI), said:

“This is a very exciting and robust paper from a highly respected group of scientists. We have known for a long time that inflammation and the proliferation of brain inflammatory cells (microglia) are important drivers of Alzheimer’s disease, but the precise inflammatory pathways have not been defined, making it extremely difficult to design therapies that suppress the disease.

“This paper shows that activation of a particular receptor on microglia, termed CSF1R, correlates with microglial proliferation and disease severity in Alzheimer’s. Critically, a well-known inhibitor of CSFR1 activation prevented microglial activation and inhibited disease development in a mouse Alzheimer’s model.

“The findings raise the realistic prospect of targeting CSFR1 activation to inhibit the development of dementia in those with the earliest signs of Alzheimer’s disease. Because drugs that inhibit CSFR1 activation are already in the clinic for other applications, this might be achievable much more quickly than starting from scratch with a new drug.”

‘Pharmacological targeting of CSF1R inhibits microglial proliferation and prevents the progression of Alzheimer’s-like pathology’ by Olmos-Alonso et al. published in Brain on Friday 8^th January. 

Declared interests

Prof. Hardy: Consults for Eisai Pharma

Dr Dallas: Received funding from ARUK and is Neuroscience Theme Lead, The Physiological Society

Dr Brown: Alzheimer’s Society provides funding for Brains for Dementia Research which supplied post mortem brain tissue for this research.

Others: None declared