Does Alzheimer’s Start in the Gut?

UW researchers have discovered that microbes in the intestines of Alzheimer’s disease patients differ from those of healthy people. Danielle Lawry

A compound produced by bacteria in most people’s digestive tracts increases the risk of developing Alzheimer’s disease and speeds up cognitive decline in dementia patients, according to a new study.

Nearly 10 years ago, researchers led by UW–Madison professors Barbara Bendlin and Federico Rey discovered that microbes in the intestines of Alzheimer’s disease patients differ from those of healthy people.

“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 gerontology in the UW School of Medicine and Public Health.

In a recent study, the researchers found that a compound called imidazole propionate (ImP) — produced in the gut by some types of bacteria — plays an important role in brain changes that result in Alzheimer’s disease and related cases of dementia.

“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.”

ImP can spread from the gut to other parts of the body, where it has been implicated in type 2 diabetes and coronary artery disease. The researchers showed that ImP that reaches the brain in mice increases the buildup of clumps of two abnormal proteins.

“That process eventually results in the death of neurons, and in humans is a key feature of Alzheimer’s disease,” Rey says.

By looking at ImP in the blood of almost 1,200 people who have participated in the Wisconsin Registry for Alzheimer’s Prevention and studies at the Wisconsin Alzheimer’s Disease Research Center, the researchers found that people with high ImP levels were far more likely to also show markers of dementia-related protein and neuron dysfunction. They identified a genetic variation, present in about 43 percent of the people in the study, linked to accumulating much higher levels of ImP in the blood.

“This genetic variation has been associated with increased Alzheimer’s risk in large genetic studies before, and now we may understand why it’s connected,” Rey says.

Further studies could reveal whether targeting ImP might be an effective treatment to reduce Alzheimer’s risk.

Published in the Winter 2026 issue