Study shows inflammation-reducing chemical prevents memory and behavioural problems in diseased mice, raising hopes for human treatment
Scientists have fresh hopes for an Alzheimer’s treatment after experiments to reduce inflammation in diseased mouse brains prevented memory and behavioural problems in the animals.
Alzheimer’s disease has long been linked to disruption in the brain’s immune system, but the latest research adds to evidence that inflammation in the brain is not so much caused by the disease, but is a driver of the disorder.
Researchers at Southampton University studied tissues from healthy human brains and others affected by Alzheimer’s disease. They found that Alzheimer’s brains had more immune cells, known as microglia, than healthy brains.
The scientists next looked at microglia in mice that had been bred to develop a condition that resembles Alzheimer’s disease. In a series of experiments reported in the journal Brain, the team injected mice with a chemical that stops microglia numbers from growing too high.
In untreated mice, the disease caused brain cells steadily to lose their connections with one another. But treated mice kept their nerve cell connections and had fewer memory and behavioural problems. Crucially, the treatment maintained the normal levels of microglia needed for a healthy brain immune system. The treatment did not, however, stop the build up of characteristic amyloid plaques in the animals’ brains.
Diego Gomez-Nicola, who led the study, said the experiments were “as close to evidence as we can get” that inflammation and microglia were important for the progression of Alzheimer’s disease. The team now intends to work with the pharmaceutical industry to find a suitable drug that can be tested in humans. The chemical given to the mice acts on a receptor found on the surface of microglia called CSFR1.
“This is a very exciting and robust paper from a highly respected group of scientists,” said Paul Morgan, director of Cardiff University’s Systems Immunity University Research Institute. “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.”
Mark Dallas, a neuroscientist at Reading University, said the discovery could explain why drugs designed to treat Alzheimer’s have so far been unsuccessful.
“While this basic science research provides strong evidence, the challenge will now be to develop medicines for people with dementia. 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,” he added.
Simon Ridley, director of research at Alzheimer’s Research UK, which co-funded the study, said: “Research like this is vital as there are currently no treatments that can stop or slow the progression of Alzheimer’s disease in the brain.”
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