New study finds genetic link between Alzheimer’s disease and disorders of the gastrointestinal tract

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

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

Alzheimer’s disease is the most common form of dementia, characterized by neurodegeneration and a progressive decline in cognitive abilities.

The disorder ranks as a topic of growing global public health importance, with far-reaching social and economic consequences for patients, their families, and society as a whole.

By 2030, more than 82 million people – and about 152 million by 2050 – are expected to suffer from Alzheimer’s disease.

While Alzheimer’s disease has no known cures and its pathogenesis is not yet clearly understood, a comprehensive assessment of its shared genetics with other diseases may provide insight into its underlying biological mechanisms. and to enhance potential therapy development efforts.

The available evidence suggests comorbidity or some form of association between Alzheimer’s disease and disorders of the gastrointestinal tract, although it is unclear whether gastrointestinal tract traits are risks for Alzheimer’s disease. Alzheimer’s or vice versa.

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

“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.”

In the study, Dr. Adewuyi and his colleagues analyzed summary data from several genome-wide association studies – each involving around 400,000 people.

They identified genomic regions and genes common to Alzheimer’s disease and disorders of the gastrointestinal tract that could potentially be the subject of further investigation, in particular the PDE4B gene (or its subtypes) that has shown promise in inflammatory diseases.

“Our 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,” said Professor Simon Laws, researcher at the Center. 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 researchers conducted further analysis of shared genetics, they discovered other important links between Alzheimer’s disease and disorders of the gastrointestinal tract, such as the role cholesterol may play.

“Abnormal cholesterol levels have been shown to be a risk for Alzheimer’s disease and intestinal disorders,” Dr. Adewuyi said.

“Examination of genetic and biological features common to Alzheimer’s disease and these intestinal disorders suggests important roles for lipid metabolism, the immune system, and cholesterol-lowering drugs.”

“Although further studies are needed on the mechanisms shared between the conditions, there is evidence that high cholesterol can transfer into 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, all of which support the potential role of abnormal lipids in Alzheimer’s disease and gut disorders.”

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

Although there is currently no known cure, the results suggest that cholesterol-lowering drugs (statins) may be therapeutically beneficial in the treatment of Alzheimer’s disease and disorders of the gastrointestinal tract.

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

“However, more studies are 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.”

The results were published in the journal Communications Biology.

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EO Adewuyi et al. 2022. Large-scale genome-wide cross-trait analysis reveals shared genetic architecture between Alzheimer’s disease and disorders of the gastrointestinal tract. Common Biol 5.691; doi:10.1038/s42003-022-03607-2

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