People with more imidazole propionate in their blood lost cognitive ground faster over repeated testing, in a study of 1,196 cognitively unimpaired adults in Wisconsin. Imidazole propionate, or ImP, is made by certain gut bacteria, and the group with high levels also showed more blood markers of Alzheimer’s-type protein buildup and neuron injury.
Barbara Bendlin of the University of Wisconsin School of Medicine and Public Health and Federico Rey of UW-Madison’s bacteriology department led the work, which also includes mouse experiments pointing the same way.
ImP: a histidine byproduct that reaches the bloodstream
The work was published as a peer-reviewed paper. The study, titled “Gut bacterial metabolite imidazole propionate potentiates Alzheimer’s disease pathology,” appeared in Nature Communications (volume 17, article 8017) on June 26, 2026. The University of Wisconsin-Madison release followed on Aug. 12. ImP forms when some gut bacteria use the amino acid histidine for energy; once made in the gut, it can enter the bloodstream. Earlier research had tied it to type 2 diabetes and coronary artery disease.
Rey made the case for why a compound from a small bacterial population can matter to the host, and for why researchers should look beyond the most abundant species in the gut: “a microbe doesn’t have to be abundant to have an impact on the host.”
The 1,196-person cohort and the decline in cognitive scores
The human data came from the Wisconsin Registry for Alzheimer’s Prevention and the Wisconsin Alzheimer’s Disease Research Center, whose participants in this analysis were cognitively unimpaired, with a mean age of 61.2. In the paper, higher plasma ImP was associated with lower scores on a cognitive composite (mPACC3) at the time of sampling, in 1,135 participants with complete data (P = 7.72e-05), and with steeper decline in those scores across repeat testing.
ImP also tracked with two blood markers of Alzheimer’s-related injury. It was positively associated with plasma phosphorylated tau 217 (P = 1.84e-05) and with neurofilament light, a marker of neuron damage (P = 2.03e-04). The association with GFAP, a marker of astrocyte reactivity, reached only a trend (P = 0.064). The UW School of Medicine and Public Health summary puts the pattern plainly: those with the highest levels had the fastest cognitive decline.
Observational associations in people not diagnosed with dementia describe decline in test scores, not the course of an established disease, which is why the finding is stated in those terms. Neither the paper nor the university releases report a diagnosis-level outcome such as conversion to dementia.
Mouse experiments, brain barrier cells and the SLC6A13 variant
The causal evidence is thinner and comes from several directions. In 5XFAD mice, a model of amyloid pathology, ImP increased the burden of amyloid-beta plaques. In PS19 P301S mice, a tau model, it increased GFAP-positive astrocytes and phosphorylation of tau at several sites. All the mice were male. In human brain endothelial cells, ImP lowered barrier resistance, and in live mice it increased leakage of Evans blue dye into the brain. In primary neurons, ImP raised a phosphorylated tau marker, pTau-AT8, more than threefold, and a GSK3 beta inhibitor reversed the effect.
A genetic angle adds to that. The variant rs7969761, an intronic change in the SLC6A13 gene on chromosome 12, is associated with higher ImP: the T allele raised levels (P = 7.3 x 10 to the minus 18) and was linked to somewhat higher Alzheimer’s risk, with an odds ratio of 1.02. A Mendelian randomization analysis estimated an odds ratio of 1.16 per standard deviation of genetically predicted ImP. About 43% of the study participants carried a variant associated with substantially higher ImP, and the researchers suspect it affects how well the kidneys clear the compound from blood.
A statin-like inhibitor, not a diet fix
The obvious reaction, cutting histidine-rich food, does not work as a plan. Bendlin said histidine is an essential amino acid found all over the diet, and that the answer is not as simple as stopping eggs or red meat. Her team instead points to a drug that lowers ImP in the blood, with statins for cholesterol as the model: people with elevated levels would take a drug, as people with elevated cholesterol do. Bendlin framed the first step as finding an inhibitor that can bring down ImP levels in the blood, and no such compound has been reported.
No such drug exists yet, and whether lowering ImP would change cognitive outcomes in people is untested. The Association of American Universities’ repost of the UW release carries the same framing, and the later wire summary adds funding from the Wisconsin Partnership Program, the NIH and the USDA.
The paper itself flags the limit that matters most: the human findings are largely observational, and the causal claim in people rests on one genetic variant with a modest effect.
This article was produced with the assistance of AI and reviewed by Morning Overview editors prior to publication.
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