Discovery of genetic connection between Alzheimer’s and gut disorders

Research continues to demonstrate the many ways the gut microbiome can influence human health, and an active area within this field centers on its role in Alzheimer’s disease (AD). A new study has furthered our knowledge of this relationship by demonstrating what’s described as a clear genetic link between the two, while also pointing to the potential for new treatments.

Carried out by scientists at Australia’s Edith Cowan University, the study is described as the first of its kind in that it makes a comprehensive assessment of the genetic link between Alzheimer’s disease and various gut disorders. This involved analysis of genetic data sourced from genome-wide studies on Alzheimer’s and gut disorders, concerning around 400,000 subjects on each.

The scientists found that sufferers of AD and gut disorders have some genes in common. While they don’t conclude that one can drive the other, the results do point to a genetic overlap that sheds light on possible shared causes. In their study, the researchers were able to identify biological pathways that were “significantly enriched” for genes related to both conditions, with cholesterol seeming to play a central role.

“Looking at the genetic and biological characteristics common to AD and these gut disorders suggests a strong role for lipids metabolism, the immune system, and cholesterol-lowering medications,” said Dr Emmanuel Adewuyi, who led the research. “Whilst further study is needed into the shared mechanisms between the conditions, there is evidence high cholesterol can transfer into the central nervous system, resulting in abnormal cholesterol metabolism in the brain.”

An example of this can be found in earlier research indicating that high cholesterol can increase permeability of the blood brain barrier, driving up cholesterol levels in the brain and fostering growth of amyloid beta, a protein linked to Alzheimer’s onset. Similarly, high cholesterol has been shown to be a risk factor for gut disorders, according to the team, and certain gut bacteria are thought to cause or even worsen these effects through chronic inflammation.

“There is also evidence suggesting abnormal blood lipids may be caused or made worse by gut bacteria (H.pylori), all of which support the potential roles of abnormal lipids in AD and gut disorders,” said Adewuyi.

While more work is needed to understand these links, the scientists do point to the potential of cholesterol-lowering medications such as statins to be useful in treating AD and gut disorders. The study also presents new markers that clinicians could screen for as a way of detecting Alzheimer’s in its early stages.

“The study provides a novel insight into the genetics behind the observed co-occurrence of AD and gut disorders,” Dr Adewuyi said. “This improves our understanding of the causes of these conditions and identifies new targets to investigate to potentially detect the disease earlier and develop new treatments for both types of conditions.”

The research was published in the journal Communications Biology.

Source: Edith Cowan University

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