Higher levels of imidazole propionate (ImP), a compound produced by some bacteria in the gut, contribute to dementia-related changes in the brain, according to a new study led by Barbara Bendlin, PhD, a professor of medicine and Federico Rey, PhD, a professor of bacteriology and medical microbiology and immunology. Ten years ago, research teams led by the two faculty members discovered that the communities of microbes living in the intestines of Alzheimer’s disease patients differ from those of healthy people. Now they have shown that when ImP reaches the brain in mice, there is an increase in the buildup of clumps of two abnormal proteins, beta-amyloid and tau. That buildup eventually results in the death of neurons, which is a key feature of Alzheimer’s disease in humans.
By looking at ImP in the blood of almost 1,200 people, researchers found that people with high levels of the compound were far more likely to show markers of dementia-related protein and neuron dysfunction, and those with the highest levels experienced the fastest cognitive decline. They also identified a genetic variation, present in about 43% of the people in the study, linked to accumulating much higher levels of ImP in the blood. The genetic variation might affect how well the kidneys filter out ImP, allowing the body to get rid of it.
Importantly, the study suggests that targeting ImP could be a way to help people avoid risk of Alzheimer’s disease and related dementias. If researchers can find an inhibitor to decrease the levels of ImP in the blood, they think it could reduce the risk of dementia and slow cognitive decline.
