Gut-Bacteria Compound Linked to Faster Alzheimer's Decline

A molecule produced by certain gut bacteria, called imidazole propionate (ImP), may help explain the long-observed link between the gut microbiome and Alzheimer's disease, according to a new study in Nature Communications by researchers at the University of Wisconsin-Madison. Higher blood levels of ImP were associated with greater Alzheimer's risk and faster cognitive decline in people already diagnosed with dementia.

Gut bacteria produce ImP while breaking down histidine, an amino acid found widely in protein-rich foods. Production varies considerably between individuals. In mice, the researchers — led by professors Barbara Bendlin and Federico Rey — found that ImP reaching the brain increased the buildup of two abnormal proteins linked to Alzheimer's, beta-amyloid and tau, a process that eventually kills neurons.

The team then measured ImP in blood samples from nearly 1,200 participants in the Wisconsin Registry for Alzheimer's Prevention and related studies at the Wisconsin Alzheimer's Disease Research Center. People with higher ImP concentrations were more likely to show markers of dementia-related protein abnormalities and neuronal dysfunction, and cognitive tests taken over time showed that those with the highest ImP levels experienced faster cognitive decline. The researchers also identified a genetic variant, present in about 43% of participants, associated with substantially higher blood ImP levels — a variant that had previously been linked to increased Alzheimer's risk in large genetic studies.

Because gut bacteria produce ImP from histidine, an amino acid essential to human health and found in many protein-rich foods, the researchers say lowering ImP through diet alone would be difficult; they instead hope to find a drug that can inhibit the compound directly, similar to how statins lower cholesterol.