Discovery of Alzheimer’s disease: genetic link confirmed with intestinal disorders

Summary: A new study reveals a genetic link between Alzheimer’s disease and several gut-related disorders. Researchers report that patients with Alzheimer’s disease and those with intestinal disorders have specific genes in common. The findings add to evidence that the gut-brain axis may play a role in the development of neurodegenerative disorders.

Source: Edith Cowan University

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 results 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.

A genetic link between Alzheimer’s disease and intestinal disorders has been discovered. Credit: Edith Cowan University

“Although further studies are needed on the mechanisms shared between the conditions, there is evidence that high cholesterol can be transferred 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 (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.

See also

This shows a diagram of the study

“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.

About this Alzheimer’s disease and genetics research news

Author: Sam Jeremy
Source: Edith Cowan University
Contact: Sam Jeremic – Edith Cowan University
Image: Image is credited to Edith Cowan University

Original research: Free access.
“Large-scale genome-wide cross-trait analysis reveals shared genetic architecture between Alzheimer’s disease and disorders of the gastrointestinal tract” by Simon Laws et al. Communications Biology


Summary

Large-scale, genome-wide cross-trait analysis reveals shared genetic architecture 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 (AD) and disorders of the gastrointestinal tract (GIT); however, their underlying mechanisms remain unclear.

Here, we analyze several summary statistics from genome-wide association studies (GWAS) (N=34,652–456,327), to assess the relationship between AD and GIT disorders. The results reveal a significant positive genetic overlap and correlation between Alzheimer’s disease and gastroesophageal reflux disease (GERD), peptic ulcer disease (PUD), gastritis-duodenitis, irritable bowel syndrome and diverticulosis, but not inflammatory bowel disease.

Cross-trait meta-analysis identifies multiple loci (Pmeta-analysis−8) shared by AD and GIT disorders (GERD and PUD) including PDE4B, BRNP3, ATG16L1, SEMA3F, HLA-DRA, SCARA3, MTSS2, PHBand TOMM40. Colocalization and gene-based analyzes reinforce these loci. Pathway-based analyzes demonstrate significant enrichment of lipid metabolism, autoimmunity, lipase inhibitors, PD-1 signaling, and statin mechanisms, among others, for AD and GIT traits.

Our results provide genetic insights into the gut-brain relationship, implying a shared but not causal genetic susceptibility to gastrointestinal disorders with AD risk.

The identified genes and biological pathways are potential targets for further investigation in AD, gastrointestinal disorders and their comorbidity.

Comments are closed.