Breakthrough Discovery Links Gut Bacteria to Alzheimer's Risk

Researchers have made a breakthrough discovery that could potentially lead to new treatments for Alzheimer's disease. According to their findings, bacteria in the digestive system may produce a molecule that increases the risk of developing Alzheimer's and accelerates cognitive decline.

The link between gut bacteria and Alzheimer's was first identified nearly a decade ago by a team led by University of Wisconsin-Madison professors Barbara Bendlin and Federico Rey. They found that people with Alzheimer's have different types of microorganisms living in their intestines compared to healthy individuals.

Bendlin, a professor of medicine at the UW School of Medicine and Public Health, has been investigating how this difference in gut bacteria affects brain health. "We've been trying to figure out how this difference in the gut perhaps leads to changes in the brain," she says.

The researchers have now focused on a specific compound produced by certain bacteria in the gut called imidazole propionate (ImP). Their study, published recently in Nature Communications , suggests that ImP may play a role in brain changes associated with Alzheimer's disease and related forms of dementia.

Research has shown that when ImP is produced in the gut, it can enter the bloodstream and reach various parts of the body. Previous studies have linked ImP to an increased risk of type 2 diabetes and coronary artery disease.

The latest study suggests that ImP may also play a role in brain changes associated with Alzheimer's disease. In laboratory experiments using mice, researchers found that when ImP reached the brain, it led to an accumulation of abnormal beta amyloid and tau proteins - two key features of Alzheimer's disease.

These abnormal protein accumulations can cause neurons to die, which is a hallmark of Alzheimer's disease in humans. The study's findings indicate that ImP may contribute to the development of this condition.

The researchers then examined blood samples from over 1,200 people participating in studies on Alzheimer's prevention and research. They found that individuals with higher levels of ImP in their blood were more likely to display biological markers associated with abnormal proteins and impaired neuron function.

These volunteers had also undergone regular cognitive testing, allowing the researchers to compare ImP levels with changes in thinking and memory over time. The results showed a clear link between high ImP levels and faster cognitive decline, as measured by these tests.

The genetic variation linked to increased Alzheimer's risk may also play a role in how effectively the kidneys remove ImP from the blood.

This could result in higher levels of the compound remaining in circulation, potentially increasing the risk of cognitive decline.

A potential new target for preventing or slowing Alzheimer's disease and related dementias has been identified by the researchers: the molecule itself.

By focusing on reducing ImP levels in the bloodstream, scientists may be able to slow down the progression of the disease.

The research was a collaborative effort involving scientists from the University of California, Los Angeles and the University of Gothenburg.

Funding for this study came from various sources, including grants from the Wisconsin Partnership Program and the National Institutes of Health, as well as support from the U.S. Department of Agriculture.

This comprehensive study laid the groundwork for further research into potential ways to slow down Alzheimer's progression by targeting ImP levels in the bloodstream.