Until recently, scientists thought Alzheimer’s disease disturbed the immune system – but a new study of mice adds to mounting evidence that it could be inflammation in the brain that drives Alzheimer’s. It suggests blocking a protein that regulates immune cells could be a way to stop the brain-wasting disease.
The study – led by the University of Southampton in the UK – is to be published in the journal Brain.
Alzheimer’s is a progressive neurodegenerative disease that, together with other forms of dementia, affects 47.5 million people worldwide and gives rise to 7.7 million new cases a year.
Dementia is a syndrome that affects memory, thinking and behavior and gradually reduces people’s ability to have a normal life and take care of themselves. Alzheimer’s disease is the most common form of dementia and likely contributes to 60-70% of cases.
The team behind the new study hopes the findings will lead to a drug that halts Alzheimer’s – a disease for which there is currently no cure and no treatments that stop or slow down its progress in the brain.
For their research, they compared brain tissue samples from healthy people with those of people of the same age with Alzheimer’s. They were particularly interested in differences in the numbers of microglia – a type of cell that, among other things, helps regulate immune responses like inflammation.
The team found that the brains of people with Alzheimer’s disease had more microglia than the brains of the healthy subjects. They also found that the molecules that regulate the cells appeared to be more active where the disease was more severe.
In another part of the study, the team investigated microglia in mice engineered to develop features of Alzheimer’s disease. As the disease progresses, the animals’ brains show increasing numbers of microglia.
They found that blocking a protein called CSF1 with an oral dose of an inhibitor prevented the rise in microglia numbers seen in the untreated mice. The inhibitor also stopped the loss of communication links between nerve cells that is a feature of Alzheimer’s.
CSF1 (colony stimulating factor 1 receptor) is a cell-surface protein that regulates microglia in the brain. Previous research in mice shows that blocking CSF1R signaling reduces microglia in the adult brain.
The team also found that Alzheimer’s mice treated with the CSF1R inhibitor showed fewer memory and behavioral problems, compared with untreated mice.
Another important finding was that the inhibitor did not reduce microglia levels below the number needed for healthy immune function, suggesting blocking CSF1R only eliminates excessive numbers of cells.
Finally, the study did not find any link between blocking CSF1R and reduction of another well-known feature of Alzheimer’s disease – build-up of toxic amyloid protein clumps in the brain. The researchers say this supports evidence from other studies that suggest several factors may be involved in disease progression.
Lead author Dr. Diego Gomez-Nicola, neuroscientist and researcher in biological sciences at Southampton, says:
“These findings are as close to evidence as we can get to show that this particular pathway is active in the development of Alzheimer’s disease.”
He says the next step is to build on these results and work with partners in industry to find a safe drug to test in humans and see if blocking the action of CSF1R has the same effect.
Meanwhile, Medical News Today recently learned that androgen deprivation therapy – a common treatment for prostate cancer that lowers levels of the male hormone testosterone – may raise the risk of developing Alzheimer’s disease later on. A study published in the Journal of Clinical Oncology found that men who had the treatment were about 88% more likely to be diagnosed with Alzheimer’s disease than men who did not have it.