Genetic link between Alzheimer’s disease and multiple bowel disorders confirmed

People with intestinal disorders may be at higher risk of developing Alzheimer’s disease (AD).

A first global study from Edith Cowan University (ECU) has confirmed the link between the two, which could lead to earlier detection and potential new treatments.

AD destroys memory and thinking ability and is the most common form of dementia.

It has no known cures and is expected to affect over 82 million people and cost US$2 trillion by 2030.

Previous observational studies have suggested a relationship between Alzheimer’s disease and disorders of the gastrointestinal tract, but what underlies these relationships was unclear – until now.

ECU’s Center for Precision Health has now provided new insight into these relationships by confirming a genetic link between Alzheimer’s disease and multiple gut disorders.

The study analyzed large genetic datasets on AD and several studies on gut disorders – each involving around 400,000 people.

Dr. Emmanuel Adewuyi, lead researcher, said this was the first comprehensive assessment of the genetic relationship between Alzheimer’s disease and multiple gut disorders.

The team found that people with AD and gut disorders shared genes, which is important for many reasons.

“The study provides new insight into the genetics behind the observed co-occurrence of Alzheimer’s disease and gut disorders,” Dr Adewuyi said.

“This improves our understanding of the causes of these conditions and identifies new targets to study to potentially detect the disease earlier and develop new treatments for both types of conditions.”

Center for Precision Health director and study supervisor Professor Simon Laws said that although the study did not conclude that gut disorders cause AD or vice versa, the results are extremely valuable.

“These findings provide further evidence supporting the concept of the ‘gut-brain’ axis, a bi-directional link between the cognitive and emotional centers of the brain and the functioning of the gut,” Professor Laws said.

Is cholesterol a key?

When researchers conducted further analysis of shared genetics, they discovered other important links between Alzheimer’s disease and gut disorders, such as the role cholesterol may play.

Dr Adewuyi said abnormal cholesterol levels are a risk for both Alzheimer’s disease and gut disorders.

“Examination of genetic and biological features common to AD and these intestinal disorders suggests an important role for lipid metabolism, the immune system and cholesterol-lowering drugs,” he said.

“Although further studies are needed on the mechanisms shared between the conditions, there is evidence that high cholesterol can be transferred to the central nervous system, leading to abnormal cholesterol metabolism in the brain.

“There is also evidence to suggest that abnormal blood lipids may be caused or worsened by gut bacteria (H.pylori), all of which support the potential role of abnormal lipids in AD and gut disorders.

“For example, high cholesterol in the brain has been linked to brain degeneration and consequent cognitive impairment.”

Hope for the future

The link to cholesterol could prove vital in the treatment of AD in the future.

Although there is currently no known cure, the study results suggest that cholesterol-lowering drugs (statins) may be therapeutically beneficial in the treatment of AD and bowel disorders.

“Evidence indicates that statins have properties that help reduce inflammation, modulate immunity and protect the gut,” Dr. Adewuyi said.

However, he said more studies were needed and patients should be assessed individually to determine if they would benefit from statin use.

Research has also indicated that diet may play a role in the treatment and prevention of Alzheimer’s disease and intestinal disorders.

“Large-scale genome-wide cross-trait analysis reveals shared genetic architecture between Alzheimer’s disease and disorders of the gastrointestinal tract” was published in Communications Biology.

Reference: Adewuyi EO, O’Brien EK, Nyholt DR, Porter T, Laws SM. Large-scale, genome-wide cross-trait analysis reveals shared genetic architecture between Alzheimer’s disease and disorders of the gastrointestinal tract. Communications biography. 2022;5(1):691. doi:10.1038/s42003-022-03607-2

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