DNA changes in Alzheimer's disease: What they mean to patients, families

A study published in Nature Communications has found that a chemical produced by certain gut bacteria may speed up the onset of Alzheimer's disease. This molecule, named imidazole propionate, is a byproduct created when gut bacteria break down histidine, an amino acid present in many foods. Elevated levels of imidazole propionate have been linked to worse cognitive decline in humans and actively contribute to neurodegeneration in animal models.

The research, led by Vaibhav Vemuganti and Jea Woo Kang from the University of Wisconsin-Madison, involved analyzing blood samples from nearly 1,200 older adults. Participants with the highest levels of imidazole propionate performed worse on cognitive tests at the beginning of the study and exhibited an earlier and more rapid decline in memory and executive function over the course of several years.

High blood levels of this chemical were also correlated with increased amounts of tau tangles and neurofilament light chain, proteins associated with Alzheimer's disease. The researchers discovered that a specific bacterial gene called urdA, which instructs gut bacteria to produce imidazole propionate, was found in several bacterial families, including certain strains of Streptococcus.

A higher abundance of these bacteria was linked to lower cognitive scores and higher Alzheimer's biomarkers in human participants. To determine if imidazole propionate directly causes Alzheimer's in humans, the team examined genetic databases and found a specific genetic variant on chromosome 12 that leads to higher natural levels of the chemical.

This genetic variant is associated with an increased risk of developing Alzheimer's disease, indicating that imidazole propionate actively promotes the condition rather than being harmless. Additionally, the researchers conducted studies on two mouse models of Alzheimer's disease. When treated with imidazole propionate, mice predisposed to amyloid plaques developed more plaques and exhibited brain inflammation, while mice predisposed to tau tangles showed severe inflammation, hyperactivity of astrocytes, and structural breakdown in nerve fibers.

The chemical was also found to damage the blood-brain barrier, allowing substances to abnormally enter the brain. Furthermore, exposure to imidazole propionate caused cultured mouse neurons to rapidly develop tau tangles, suggesting a direct cause-and-effect relationship between this gut metabolite and Alzheimer's disease.