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, its underlying mechanisms are unclear. New analysis of genome-wide association studies demonstrates significant and positive 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 and others. analyzed various 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 prevalent form of dementia, characterized by neurodegeneration and a progressive decline in cognitive ability.
The disorder is classified as an issue of growing importance for global public health with consequences of wide adverse social and economic impact on those who suffer from it, their families and society in general.
By 2030, more than 82 million people (and about 152 million by 2050) are expected to have Alzheimer’s disease.
Although Alzheimer’s disease has no known curative treatments, and its pathogenesis is not yet clearly understood, a comprehensive assessment of its shared genetics with other diseases may provide a deeper understanding of its underlying biological mechanisms and improve therapeutic development efforts. potentials.
Available evidence suggests comorbidity or some form of association between Alzheimer’s disease and gastrointestinal tract disorders, although it is unclear whether gastrointestinal tract traits are risks for Alzheimer’s disease or vice versa.
“Our study provides novel insight into the genetics behind the observed co-occurrence of Alzheimer’s disease and intestinal disorders,” said Dr. Emmanuel Adewuyi, a researcher with the Center for Precision Health and the Genomics and Translation Collaborative Group at the Edith Cowan University.
“This improves our understanding of the causes of these conditions and identifies new targets to investigate to potentially detect 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 involving approximately 400,000 people.
They identified genomic regions and genes, shared by Alzheimer’s disease and disorders of the gastrointestinal tract, that may 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 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 gut,” said Professor Simon Laws, Research Fellow at the Centre. for Precision Health and the Edith Cowan University Genomics and Translation Collaborative Group, and Curtin University’s Curtin Health Innovation Research Institute.
When the researchers did more analysis on shared genetics, they found other important links between Alzheimer’s disease and disorders of the gastrointestinal tract, such as the role that cholesterol may play.
“Abnormal cholesterol levels have been shown to be a risk for both Alzheimer’s disease and intestinal disorders,” said Dr. Adewuyi.
“Looking at genetic and biological features common to Alzheimer’s disease and these intestinal disorders suggests an important role for lipid metabolism, the immune system, and cholesterol-lowering drugs.”
“While more study is needed on shared mechanisms between the conditions, there is evidence that high cholesterol can be transferred to the central nervous system, resulting in 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 potential roles for abnormal lipids in Alzheimer’s disease and intestinal disorders.”
“For example, elevated cholesterol in the brain has been linked to brain degeneration and subsequent cognitive decline.”
While there are currently no known curative treatments, the findings suggest cholesterol-lowering medications (statins) could 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,” said Dr. Adewuyi.
“However, more studies are needed and patients needed to be evaluated individually to judge whether they would benefit from statin use.”
“The research also indicated that diet could play a role in the treatment and prevention of Alzheimer’s disease and intestinal disorders.”
the recommendations were published in the magazine Communications Biology.
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EO Adewuyi and others. 2022. A large-scale cross-genome trait analysis reveals a shared genetic architecture between Alzheimer’s disease and disorders of the gastrointestinal tract. common biol 5, 691; doi: 10.1038/s42003-022-03607-2