Immunological Anomaly Causes Alzheimer's, Study Finds

Alzheimer's disease may have its causes linked to an abnormality in the immune system, which originally has the function of protecting the body from external invaders. The conclusion is from a new study by scientists at Duke University (USA) who also suggest a new strategy for treating the disease.

The paper, published Tuesday in the Journal of Neuroscience, shows that in individuals with Alzheimer's, certain immune cells begin to abnormally consume an important nutrient, arginine, decreasing their presence in the brain and triggering it. the disease.

From a mouse experiment, the researchers showed that it is possible to block this process with a drug, reversing in animals the memory loss caused by Alzheimer's. According to the authors, increasing evidence indicates that the immune system has a role in Alzheimer's disease, but the exact influence remains a mystery.

In the new study, they were able to demonstrate that the lack of arginine, an amino acid present in most proteins in the body, directly affects the evolution of the disease. "If arginine consumption is so important to the Alzheimer's process, maybe we can block it and reverse the disease, " said study author Carol Colton of Duke University School of Medicine.

The mice used in the research, created a few years ago to allow the study of the disease, had some genes altered so that their immune system became similar to human. Moreover, the animals were designed to present the main characteristics of Alzheimer's carriers: loss of neurons, behavioral changes and the presence in the brain of plaques and tangles of certain proteins.

Throughout the life of the mice, the team of scientists looked for immunological anomalies and found that most components of the immune system showed no quantitative changes. The exception was a type of immune cell known as microglia - which are usually the first cells to respond to Alzheimer's disease.

By isolating these cells and analyzing their genetic activity, scientists have observed an increase in the expression of genes associated with suppression of the immune system - that is, they decrease their activity. "This is surprising because suppression of the immune system is not what we thought would happen in Alzheimer's disease, " said lead author Matthew Kan, a postdoctoral fellow at Colton's lab.

According to him, before the study, scientists thought the opposite was true: the brain should release molecules involved in building the immune system, which should exacerbate its action, damaging the brain. With the microglia modification, the researchers found a large increase in the presence of arginase - an enzyme that breaks arginine molecules - in the brain regions involved with memory, in the same areas where neurons died.

According to them, with the increase of arginase, the microglia consumes an exaggerated amount of arginine. Scientists blocked the action of arginase using a drug known as DFMO before symptoms manifested in mice. They then observed a reduction in microglia modifications and plaque development in brain proteins.

Also, the mice did better on memory tests. "All of this suggests that if we can block this local process of arginine deprivation, we can protect - at least mice - from Alzheimer's disease, " said Kan. DFMO was synthesized 20 years ago and has been studied in human clinical trials for the treatment of some cancers. But the drug had not yet been tested as a potential therapy for Alzheimer's disease.

In the study, Colton's group administered the drug before symptoms appeared. Now they plan to study if DFMO can treat the consequences of Alzheimer's before they appear. According to Colton, although it has been found that arginine deficiency is linked to Alzheimer's disease, taking amino acid supplements is not an alternative to prevention.

According to him, a dense mesh of cells and blood vessels determines the amount of arginine that enters the brain. So even if a patient eats more arginine, there is no guarantee that it will go to the brain sites that need the amino acid.

By Fábio de Castro, Sao Paulo

Via InAbstract