A new study has revealed that a compound produced by bacteria in the gut may increase the risk of Alzheimer's disease and accelerate cognitive decline in patients, making it a promising target for developing future treatments.
This discovery goes back to previous research conducted by a team from the University of Wisconsin-Madison about a decade ago, in which they noticed a difference in the composition of gut microbes between Alzheimer's patients and healthy people, and since then they have been trying to understand how this difference can lead to changes in the brain.
In the current study, researchers focused on the compound imidazole propionate (ImP), which is produced by certain types of bacteria in the gut, and found that it plays a key role in brain changes associated with Alzheimer's. Although the bacteria that produce it are present in a large percentage of people, they are not abundant in most of them, but the researchers discovered that the microbe does not need to be abundant to affect the health of the host.
Experiments on mice have shown that ImP reaching the brain increases the accumulation of beta-amyloid and tau proteins, abnormal protein clumps that lead to the death of nerve cells and are a hallmark of Alzheimer's disease in humans.
Analyzing blood samples from about 1,200 participants in previous studies, the team found that people with high levels of ImP were much more likely to show signs of protein and nerve cell dysfunction associated with dementia, and they also experienced faster cognitive decline.
The researchers also identified a genetic variation present in about 43% of the participants, associated with higher levels of ImP in the blood. This variation has previously been linked to an increased risk of Alzheimer's in large genetic studies, but the new study offers a possible explanation for this association through its effect on the kidneys' ability to filter and eliminate the compound.
The most significant implication of the study is that ImP could be a target for Alzheimer's prevention. However, the challenge lies in the fact that bacteria produce this compound from an essential amino acid called histidine, which is found in many protein-rich foods, making it difficult to avoid through diet. Researchers believe that narrowing down the target to a single molecule opens the door to developing drugs similar to statins used to lower cholesterol. A drug inhibitor could reduce ImP levels in the blood, potentially lowering the risk of Alzheimer's and slowing cognitive decline in a large segment of the population.
The study was published in the journal Nature Communications.
