Gut Bacteria Make a Molecule That Speeds Up Alzheimer's
A University of Wisconsin-Madison team measured imidazole propionate, a compound gut bacteria make from histidine, in almost 1,200 people and linked it to faster memory decline.
Gut bacteria in a large share of people make a compound that enters the bloodstream, and a higher level of it tracks with faster memory decline and more frequent dementia biomarkers. The compound is called imidazole propionate, and it forms when certain gut bacteria break down the amino acid histidine. The study was led by researchers at the University of Wisconsin-Madison, working with collaborators from the University of California, Los Angeles and the University of Gothenburg. It was published in the journal Nature Communications under the digital object identifier 10.1038/s41467-026-74744-z, dated June 26, 2026 according to Crossref registry metadata. The university issued a statement on the findings on August 12.
Researchers already knew that the gut bacteria of people with Alzheimer’s disease differ from those of healthy people. Barbara Bendlin, a professor of gerontology at the university’s medical school, and Federico Rey, a professor of bacteriology, showed that nearly a decade ago. What was missing was the path connecting that difference in the gut to changes in the brain.
We’ve been trying to understand ever since how that difference in the gut might lead to changes in the brain.
That is how Bendlin describes the decade of work that preceded this study.
What was measured
The analysis drew on almost 1,200 participants in the Wisconsin Registry for Alzheimer’s Prevention and the Wisconsin Alzheimer’s Disease Research Center studies, people who had no cognitive impairment when their monitoring began. Researchers measured their blood levels of imidazole propionate and compared them against dementia biomarkers and the results of cognitive tests those volunteers took over several years. In people with high levels of the compound, markers of pathological proteins and disrupted neuron function turned up markedly more often, and their memory declined faster. The paper’s first author is Vaibhav Vemuganti.
The bacteria that make the compound aren’t abundant, and that turns out to be part of the point.
Bacteria that produce imidazole propionate are present in a large share of people, but in most of them they aren’t especially abundant.
But something we’ve learned over the years is that a microbe doesn’t need to be abundant to have an effect on its host.
Rey said both sentences in the university’s statement. Through metagenomic analysis of the samples, the team found gut bacteria carrying genes similar to urocanate reductase, the enzyme that makes the compound, and how common those bacteria were lined up with the participants’ cognitive test results.
Mice and genetics
In mice, giving the compound over a long stretch increased the buildup of beta amyloid and tau protein and raised the permeability of the blood-brain barrier. That is the part of the study that offers a mechanism, not just a statistical link.
That process ultimately leads to neuron death, which in humans is a defining feature of Alzheimer’s disease.
The team also found a genetic variant linked to markedly higher levels of the compound building up in the blood, present in about 43 percent of study participants. The authors’ hypothesis is that this variant affects how well the kidneys clear the compound from the body. The same variant had already turned up in large genetic studies as linked to a higher risk of Alzheimer’s disease, without an explanation for why.
Can diet fix this
Not really. Histidine, the raw material bacteria use to make imidazole propionate, is an essential amino acid found in many foods, especially protein-rich ones.
Improving your diet overall would probably help. But it’s not as simple as saying stop eating eggs, or don’t eat so much red meat.
That’s why the authors’ interest turns instead to a drug, and Bendlin compares the idea to something already in use for decades.
It could be like cholesterol, where people with high cholesterol take a drug, a statin, that lowers their risk of heart disease.
No such inhibitor exists yet. The work was funded by the Wisconsin Partnership Program, the National Institutes of Health (NIH) through seven grants, and the United States Department of Agriculture (USDA).
What this study doesn’t prove
The human portion of the study is observational. It shows that a high level of the compound goes along with faster memory decline, not that it causes it. The causal part comes from mice, and a mouse model of Alzheimer’s disease is not a human being, and many findings at that stage have not survived the jump to clinical trials. The genetic link is correlational, and the explanation involving kidney clearance is the authors’ hypothesis, not a measured fact.
It’s also worth noting that imidazole propionate isn’t a molecule that concerns only the brain. It has previously been linked to type 2 diabetes and coronary disease, which leaves open the question of how much of its effect on neurons is direct, and how much runs indirectly through the body’s metabolic and vascular state. We have previously covered another line of research into the same disease, one that targets amyloid buildup through estrogen, and the two lines of research don’t rule each other out.
