A molecule made by bacteria in the digestive system may increase the risk of Alzheimer's disease and accelerate cognitive decline in people with dementia, according to new research. The finding could point scientists toward a potential treatment strategy aimed at lowering Alzheimer's risk. Nearly a decade ago, a research team led by University of Wisconsin-Madison professors Barbara Bendlin and Federico Rey found that the mix of microorganisms living in the intestines differs between people with Alzheimer's disease and healthy individuals.
"Since then, we've been trying to figure out how this difference in the gut perhaps leads to changes in the brain," says Bendlin, a professor of medicine in the UW School of Medicine and Public Health. A Gut Molecule With Effects Beyond the Intestines In a recent study published in the journal Nature Communications, Bendlin, Rey and their collaborators focused on imidazole propionate (ImP), a compound produced by certain bacteria in the gut. Their findings suggest that ImP may contribute to brain changes involved in Alzheimer's disease and related forms of dementia.
ImP production varies considerably from person to person. Some people appear to generate relatively large amounts, while others produce very little. "ImP-producing bacteria are present in a large fraction of people, but they're not very abundant in most people," says Rey, a UW-Madison professor of bacteriology.
"But something we have learned over the years is that a microbe doesn't have to be abundant to have an impact on the host." Once produced in the gut, ImP can enter the circulation and reach other parts of the body. Previous research has linked the compound to type 2 diabetes and coronary artery disease. The new study suggests that its effects may also extend to the brain.
In mice, researchers found that ImP reaching the brain increased the accumulation of abnormal beta amyloid and tau proteins, two major hallmarks associated with Alzheimer's disease. "That process eventually results in the death of neurons, and in humans is a key feature of Alzheimer's disease," Rey says. Higher ImP Levels Linked to Faster Cognitive Decline The researchers then examined blood samples from almost 1,200 people enrolled in the Wisconsin Registry for Alzheimer's Prevention and studies conducted through the Wisconsin Alzheimer's Disease Research Center.
Participants with higher concentrations of ImP in their blood were much more likely to show biological markers associated with abnormal proteins and impaired neuron function in dementia. Because the volunteers had also completed cognitive testing over time, the researchers were able to compare ImP levels with changes in thinking and memory. "And because we have the results of cognitive tests these volunteers took over time, we can see that the people with the highest ImP levels also experienced much faster cognitive decline," Rey says.
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