- Studies have suggested that gastrointestinal health and Alzheimer’s disease (AD), the most common form of dementia worldwide, may be connected.
- A recent Australian study has now identified a genetic link between Alzheimer’s disease and several gut disorders.
- Many of the genes the scientists identified are involved in lipid metabolism, pointing to statins—which are used to control cholesterol—as a potential treatment for both AD and gut disorders.
- The findings might also help doctors diagnose AD earlier, allowing better control of symptoms.
Alzheimer’s disease (AD) is the most common form of dementia in older adults. According to the World Health Organization, 60-70% of dementia cases may be caused by AD, the seventh leading cause of death in the United States.
AD is incurable, but there are treatments that may slow disease progression or alleviate the symptoms. Medications are more effective if they are started early, but diagnosis can take some time, during which the disease can progress without treatment.
A recent study developed an MRI-based machine learning system that may help with early diagnosis. Now, a finding from a team in Australia has suggested another possible route to earlier diagnosis and treatment of AD.
The researchers found genetic links between multiple gut disorders and AD, which, according to lead researcher Dr. Emmanuel Adewuyi “identifies new targets to investigate to potentially detect the disease earlier and develop new treatments for both types of conditions.”
The study, led by researchers from Edith Cowan University, Perth, Western Australia, is published in Communications Biology.
Link to gut disorders
Hippocrates of Kos (c.460-377 BCE) is reputed to have said “All disease begins in the gut.” Increasingly, research is suggesting that the ancient Greek physician may have been right, at least in the case of several diseases.
Previous research studies on the gut-brain axis found that the gut microbiome may have an impact on the development of AD. In particular, some studies suggest that bacteria in the gut microbiota could influence the production of proinflammatory cytokines associated with AD pathogenesis.
A review of research studies on this topic concluded that “The convergence of gut-derived inflammatory response together with aging and poor diet in the elderly contribute to the pathogenesis of AD”.
Shared genes
The researchers of this new study set out to find out genetic associations underlying this observed association between the gut and AD. They analyzed genetic data from 15 large genome studies, most involving more than 400,000 people, containing information from AD and gut disorders.
They found certain genes were associated with having both AD and certain gut disorders—such as gastroesophageal reflux disease (GERD), peptic ulcer disease (PUD), gastritis-duodenitis, irritable bowel syndrome, and diverticulosis.
Although the researchers found significant genetic overlap and correlation between Alzheimer’s and some gastrointestinal disorders, they did not find evidence for a causal association.
The study’s senior author Prof. Simon Laws, the director of the Centre for Precision Health at Edith Cowan University, says that although the study did not find that gut disorders caused AD or vice versa, the findings were 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.”
Their study highlighted the genetic association of AD with not only gastrointestinal disorders but also the gut microbiome, reinforcing the findings of previous studies.
Commenting on the findings, the American Geriatrics Society said the study not only reveals a genetic link between Alzheimer’s disease and several gut-related disorders but that “the findings add to the evidence the gut-brain axis may play a role in the development of neurodegenerative disorders.”
Lipids, immunity, and Alzheimer’s
The researchers also looked at the biological pathways in which these genes involved in both disorders acted, and found an overrepresentation of lipid-related and immune system-related pathways. Previous research has found a connection between the disruption of lipid homeostasis and AD.
This finding that involves lipid-related pathways, including cholesterol metabolism and transport, may suggest an association between abnormal cholesterol, gut disorders, and AD, as Dr. Adewuyi explained:
“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.”
‘[E]levated cholesterol in the brain has been linked to brain degeneration and subsequent cognitive impairment,” he added.
Their findings suggest that drugs to control lipid homeostasis and inflammation may be potential treatments for AD. So, the authors suggest that cholesterol-lowering medications (statins) may prove useful in treating both conditions.
Early diagnosis
Dr. Mansi Shah, a licensed clinical integrative pharmacist, certified functional medicine practitioner, and CEO of the Functional Wellness Network, said the findings could help scientists develop new treatments.
“The study found that the risk of developing AD is increased in individuals with gastrointestinal disorders and that the two conditions share common genetic risk factors. The findings of this study may help to improve our understanding of the causes of AD and lead to the development of new treatment strategies,” she told MNT.
The study states that while the findings do not indicate that AD and gastrointestinal tract disorders will always co-occur, it reveals a possible “shared biology.”
“Thus, early detection of AD may benefit from probing impaired cognition in GIT disorders,” the authors conclude.
Perhaps an awareness of this genetic association might lead physicians to assess people with gut disorders and cognitive impairment, leading to earlier diagnosis of AD in some.
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