Arginine deprivation linked to Alzheimer’s disease in mice

Posted on 14th April 2015

Researchers at Duke University in the US have completed a mouse study which suggests that the amino acid arginine could be involved in the body’s response to Alzheimer’s disease. The study is published on 14 April in the Journal of Neuroscience.

There is growing research evidence linking the immune system to the development of Alzheimer’s disease. While usually acting as a defence mechanism to keep the body safe from infection or damage, current belief within the research community is that sustained activation of the immune system in Alzheimer’s could be detrimental and drive the disease to get worse.

The US research team studied a particular type of immune cell called microglia in mice bred to develop features of Alzheimer’s disease. These mice were shown to have higher numbers of microglia in their brains compared to normal mice. While microglia normally play a protective role, ramping up inflammatory signals to mobilise other armies of immune cells, research suggests they may switch to being more harmful during the course of Alzheimer’s.

The researchers isolated microglia from the mice and studied which genes were turned up or down, giving them an idea of what the cells were doing. They found that some of the genes most ramped up in these immune cells were those that dampen down, rather than fire up, the immune system. This finding went against previous suggestions that the detrimental effects of microglia could be due to their over-stimulation of the immune system. The team also found lower levels of the amino acid arginine in the brain due to higher levels of a protein called arginase, which breaks down arginine. The authors propose that the lower levels of arginine in the brain could contribute to the death of nerve cells and neurodegeneration.

The team then went on to treat mice with a chemical difluoromethylornithine (DFMO), which blocks the breakdown of arginine, and found fewer microglia and fewer hallmark Alzheimer’s plaques in the brains of the mice. The mice that had been treated with DFMO also performed better on memory tests than their untreated littermates. The drug has been explored as a potential treatment for cancer but has not, as yet, been implicated in the treatment of Alzheimer’s.

Dr Laura Phipps of Alzheimer’s Research UK, the UK’s leading dementia research charity, said:

“This interesting study sheds more light on the mechanisms of immune system involvement in Alzheimer’s, adding important insight to a growing body of research in this area. The research is in mice, so it will be important to build on the findings with further studies in humans. Clinical trials are essential before any potential new treatment can be given to people, but these early findings could open new doors for future treatment development for Alzheimer’s.

“The study suggests that low levels of arginine in the brain could contribute to the death of nerve cells in Alzheimer’s, but there is much more we still need to understand about how and why nerve cells die in the disease. Arginine is produced by the body, as well as being consumed through diet, and while it was implicated in this research study, the findings do not suggest that supplementation of the amino acid could mirror the benefits seen in these mice. Current research suggests that the best way to maintain a healthy brain throughout life is to ensure a balanced diet, not smoke, keep mentally and physically active and exercise regularly, and keep blood pressure and cholesterol in check.”

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