Researchers at the University of Wisconsin-Madison have identified a gut bacterial compound, imidazole propionate (ImP), that may raise Alzheimer's risk and speed cognitive decline. The study, published in Nature Communications, builds on earlier work showing gut microbe differences between people with Alzheimer's and healthy individuals. In mice, ImP reaching the brain increased buildup of beta amyloid and tau proteins, key hallmarks of the disease.
The team then analyzed blood samples and cognitive test results from almost 1,200 participants in Wisconsin Alzheimer's studies. Those with the highest ImP concentrations showed more biological markers of dementia and experienced much faster cognitive decline over time. The researchers also found a genetic variation, carried by about 43% of participants, that was associated with substantially higher ImP levels—possibly by affecting how well the kidneys clear the compound from blood.
The findings suggest ImP could become a target for preventing or slowing dementia, similar to how statins lower cholesterol to reduce heart disease risk. However, the researchers caution that reducing ImP through diet alone is not straightforward, since gut bacteria produce it from histidine, an essential amino acid found in many protein-rich foods. Instead, they envision developing an inhibitor that lowers ImP in the bloodstream, which could one day help reduce Alzheimer's risk and cognitive decline for a significant number of people. The study was supported by grants from the Wisconsin Partnership Program, the National Institutes of Health, and the U.S. Department of Agriculture. As a single study, the findings will need replication before any clinical{