Scientists have linked a metabolite of intestinal bacteria to Alzheimer's disease
Researchers have found a link between imidazole propionate (ImP) and changes characteristic of Alzheimer's disease. In mice, an excess of the metabolite was accompanied by the accumulation of pathological proteins in the brain, and in humans, its high blood levels were associated with a faster decline in cognitive functions. About how an intestinal bacterial compound is associated with the risk of Alzheimer's disease, in the Izvestia article.
Why did scientists study ImP
The study was published in the scientific journal Nature Communications (NC). Almost 10 years ago, a team of scientists from the University of Wisconsin-Madison discovered differences in the composition of intestinal microorganisms in people with Alzheimer's disease and healthy participants.
Barbara Bendlin, Professor of Medicine at the University of Wisconsin-Madison School of Medicine and School of Public Health
Since then, we have been trying to understand how this difference in the gut can lead to changes in the brain.
In the new work, the researchers focused on imidazole propionate, a metabolite produced by some intestinal bacteria. Its amount can vary significantly from person to person. At the same time, bacteria capable of producing ImP are found in many people, although they usually do not make up a significant part of the intestinal microbiota.
What the experiment on mice showed
After formation in the intestine, ImP can enter the bloodstream and spread throughout the body. Scientists have tested whether the substance can affect the brain.
In experiments on mice, the researchers found that ImP reaching the brain was accompanied by an increase in the accumulation of pathological forms of beta-amyloid and tau protein. These proteins are considered to be one of the key signs of pathological changes in Alzheimer's disease.
Federico Rey, Professor of Bacteriology at the University of Wisconsin-Madison
This process eventually leads to the death of neurons, which in humans is a key feature of Alzheimer's disease.
Thus, the experimental results indicated a possible mechanism linking the metabolite of intestinal bacteria with changes in the nervous system.
High levels of ImP were associated with rapid memory loss.
The researchers then examined blood samples from almost 1,2 thousand people who participated in Alzheimer's prevention studies and the work of the Wisconsin Alzheimer's Disease Research Center.
Participants with higher concentrations of ImP in their blood were more likely to show biological signs associated with abnormal proteins and impaired neuron function in dementia. In addition, the volunteers underwent cognitive tests over time, which allowed the scientists to compare the levels of the substance with changes in thinking and memory.
Federico Rey
And because we have the results of cognitive tests that these volunteers took over a period of time, we see that people with the highest levels of ImP also experienced much faster cognitive decline.
The data obtained not only linked the level of the metabolite with the already existing biological signs of the disease, but also showed its connection with the subsequent dynamics of cognitive functions.
A genetic trait increased the level of the substance in the blood
The scientists also found a genetic variant that was associated with a significantly higher concentration of ImP in the blood. This option was identified in about 43% of the study participants.
The researchers suggest that a genetic trait may affect the efficiency of ImP elimination by the kidneys and thereby determine how much of the substance remains in the bloodstream. At the same time, the same genetic variant has previously been associated with an increased risk of Alzheimer's disease in large genetic studies.
Federico Rey
This genetic variant has already been linked to an increased risk of Alzheimer's disease in large genetic studies, and now we may understand the reason for the link.
Thus, the genetic data complemented the results of blood tests and animal experiments, indicating a possible link between the level of ImP and the risk of pathological changes.
Why has ImP become a separate research area
ImP is formed when intestinal bacteria use histidine, an amino acid essential to the body and found in many foods, especially those rich in protein. Therefore, the researchers note, simply excluding certain foods from the diet will not necessarily significantly reduce the level of the metabolite.
The researchers believe that the discovery of a specific metabolite and its associated genetic variant provides an opportunity to more accurately study the mechanism that may be associated with the development of Alzheimer's disease. However, the results obtained so far do not mean that ImP is the only cause of the disease.
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