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Consistent with the concept of the gut-brain phenomenon, observational studies suggest a relationship between Alzheimer’s disease and gastrointestinal tract disorders. However, their underlying mechanisms are unclear. A new analysis of genome-wide association studies demonstrates a positive significant genetic overlap and correlation between Alzheimer’s disease and gastroesophageal reflux disease, peptic ulcer disease, gastritis-duodenitis, irritable bowel syndrome and diverticulosis, but not inflammatory bowel disease.

Adewuyi et al. analyzed several genome-wide association studies (GWAS) summary statistics to assess the relationship of Alzheimer’s disease and gastrointestinal tract disorders. Image credit: Darryl Leja, National Human Genome Research Institute, National Institutes of Health.

Alzheimer’s disease is the most prevalent form of dementia, characterised by neurodegeneration and a progressive decline in cognitive ability.

The disorder ranks as a subject of increasing global public health importance with consequences for wide-ranging social and economic adverse impacts on sufferers, their families, and the society at large.

By the year 2030, over 82 million people — and about 152 million by 2050 — are projected to suffer from Alzheimer’s disease.

While Alzheimer’s disease has no known curative treatments, and its pathogenesis is yet to be clearly understood, a comprehensive assessment of its shared genetics with other diseases can provide a deeper understanding of its underlying biological mechanisms and enhance potential therapy development efforts.

The available evidence suggests comorbidity or some forms of association between Alzheimer’s disease and gastrointestinal tract disorders, although it is not clear whether gastrointestinal tract traits are risks for Alzheimer’s disease or vice versa.

“Our study provides a novel insight into the genetics behind the observed co-occurrence of Alzheimer’s disease and gut disorders,” said Dr. Emmanuel Adewuyi, a researcher in the Centre for Precision Health and the Collaborative Genomics and Translation Group at Edith Cowan University.

“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.”

In the study, Dr. Adewuyi and colleagues analyzed summary data from several genome-wide association studies — each of about 400,000 people.

They identified genomic regions and genes, shared by Alzheimer’s disease and gastrointestinal tract disorders that may potentially be targeted for further investigation, particularly, the PDE4B gene (or its subtypes) which has shown promise in inflammatory diseases.

“Our findings provide further evidence to support the concept of the ‘gut-brain’ axis, a two-way link between the brain’s cognitive and emotional centres, and the functioning of the intestines,” said Professor Simon Laws, a researcher in the Centre for Precision Health and the Collaborative Genomics and Translation Group at Edith Cowan University, and the Curtin Health Innovation Research Institute at Curtin University.

When the researchers conducted further analysis into the shared genetics, they found other important links between Alzheimer’s disease and gastrointestinal tract disorders — such as the role cholesterol may play.

“Abnormal levels of cholesterol were shown to be a risk for both Alzheimer’s disease and gut disorders,” Dr. Adewuyi said.

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

“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, all of which support the potential roles of abnormal lipids in Alzheimer’s disease and gut disorders.”

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

While there are currently no known curative treatments, the findings suggest cholesterol lowering medications (statins) could be therapeutically beneficial in treating both Alzheimer’s disease and gastrointestinal tract disorders.

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

“However, there is 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’s disease and gut disorders.”

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