Scientists have added yet another piece to the frustratingly complex Alzheimer’s puzzle with the discovery that immune cells could play a rather unexpected role in the development of the disease.
According to new research in mice, a certain type of brain immune cell seems to go rogue in those with the disease, abnormally consuming an essential nutrient called arginine. Promisingly, when the researchers prevented this process from occurring with a previously developed drug, mice with models of the disease did not experience memory loss or characteristic brain changes associated with Alzheimer’s, potentially suggesting a novel treatment avenue for humans. The study has been published in the Journal of Neuroscience.
Alzheimer’s is a highly complex, multi-faceted disease which, despite years of intense research, is still far from being fully understood by scientists. While we have learned a lot by studying the brains of human Alzheimer’s patients, mice have become an invaluable tool in furthering our knowledge of this disease. That’s because scientists can genetically alter them so that they model human Alzheimer’s, meaning scientists can investigate the changes that occur with the disease.
A few years ago, scientists from Duke University engineered a strain of mice which not only developed the hallmark changes that occur in Alzheimer’s patients, such as brain plaques and behavioral changes, but also had a similar immune system to humans. With these animals, the researchers could observe what happens to the brain at the onset of disease and monitor its progression over time.
As the immune system has been suggested to play a role in Alzheimer’s, the scientists were interested in looking for immune abnormalities which co-occurred with the disease. While they didn’t observe any significant alterations in the number of immune components present, they found that a type of brain immune cell, known as microglia, began to divide and exhibit changes at the onset of disease.
After isolating them in the lab, they observed elevated expression of genes which act to dampen the immune system, and decreased expression of genes which act to boost it. This was particularly surprising given the fact that several lines of evidence suggest that immune cells are inappropriately active in Alzheimer’s brains and actually promote the death of neurons.
Another interesting finding was that the microglia were also producing abnormally high amounts of an enzyme which breaks down the amino acid arginine, an important nutrient which can be obtained from food. When the researchers blocked the activity of this enzyme with a drug administered before the onset of symptoms, the mice developed fewer plaques and also performed better on memory tests.
“All of this suggests to us that if you can block this local process of amino acid deprivation, then you can protect -- the mouse, at least -- from Alzheimer’s disease,” study author Matthew Kan said in a news-release.
While these results are encouraging, they only tested the drug on animals before symptoms had appeared, which isn’t very useful for us, so the researchers plan to investigate whether administering it later on in the disease is effective.