Alzheimer disease breakthrough: Genetic link to gut disorders confirmed

People with gut disorders may be at greater risk of developing Alzheimer disease. A world-first Edith Cowan University (ECU) study has confirmed the link between the two, which could lead to earlier detection and new potential treatments.

Alzheimer disease destroys memory and thinking ability and is the most prevalent form of dementia. It has no known curative treatments and is expected to affect more than 82 million people and cost US$2 trillion by 2030.

Previous observational studies have suggested a relationship between Alzheimer disease and gastrointestinal tract disorders, but what underpins these relationships had been unclear – until now. ECU’s Centre for Precision Health has now provided new insights into these relationships by confirming a genetic link between Alzheimer disease and multiple gut disorders.

The study analyzed large sets of genetic data from Alzheimer disease and several gut-disorder studies – each of about 400,000 people.

Research lead Dr Emmanuel Adewuyi said it was the first comprehensive assessment of the genetic relationship between Alzheimer disease and multiple gut disorders.

The team discovered people with Alzheimer disease and gut disorders have genes in common - which is important for many reasons. “The study provides a novel insight into the genetics behind the observed co-occurrence of Alzheimer disease 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.”

Centre for Precision Health director and study supervisor Professor Simon Laws said whilst the study didn’t conclude gut disorders cause Alzheimer disease or vice versa, the results are immensely valuable.

“These findings provide further evidence to support the concept of the "gut-brain" axis, a two-way link between the brain’s cognitive and emotional centers, and the functioning of the intestines,” Professor Laws said.

Is cholesterol a key?

When researchers conducted further analysis into the shared genetics, they found other important links between Alzheimer disease and gut disorders – such as the role cholesterol may play.

Dr Adewuyi said abnormal levels of cholesterol were shown to be a risk for both Alzheimer disease and gut disorders.

“Looking at the genetic and biological characteristics common to Alzheimer disease and these gut disorders suggests a strong role for lipids metabolism, the immune system, and cholesterol-lowering medications,” he said.

“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.

“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 Alzheimer disease and gut disorders.

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

Hope for the future

The cholesterol link could prove vital in treating Alzheimer disease in the future. While there are currently no known curative treatments, the study’s findings suggest cholesterol-lowering medications (statins) could be therapeutically beneficial in treating both Alzheimer disease and gut disorders.

“Evidence indicates statins have properties which help reduce inflammation, modulate immunity, and protect the gut,” Dr Adewuyi said. However, he said there was a need for more studies and patients needed to be assessed individually to judge whether they would benefit from statin use.

The research also indicated diet could play a part in treating and preventing Alzheimer disease and gut disorders. 

'A large-scale genome-wide cross trait analysis reveals shared genetic architecture between Alzheimer's disease and gastrointestinal tract disorders' was published in Communications Biology.

Source: News Release
Edith Cowan University
July 18, 2022