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New Alzheimer’s study zeroes in on a gut-brain genetic nexus

New Alzheimer’s study zeroes in on a gut-brain genetic nexus

While Alzheimer’s neurological link has long been known, its intersection with the gut-brain axis is yet to be fully understood
gut brain axis
Representational image | Shutterstock

A newly published Australian study with a path-breaking outcome is being seen by medical scientists as a beacon of hope for early detection of Alzheimer’s disease and a potential therapy for it.  

Its core conclusion is that people with Alzheimer’s disease (AD) and gut disorders have genes in common.  

Of all the Alzheimer’s research to date, this “was the first comprehensive assessment of the genetic relationship between AD and multiple gut disorders,” according to the study lead, Emmanuel O. Adewuyi, of the Centre for Precision Health, Edith Cowan University, Australia. 

The study for the first time concludes that individuals suffering from gastrointestinal disorders may be at a relatively higher risk of developing Alzheimer’s disease. The study was published as recently as in July this year.  

“The study provides a novel insight into the genetics behind the observed co-occurrence of AD and gut disorders,” says Dr Adewuyi. 

The large genetic data were derived from well-known databases, repositories, and large research consortia or groups. 

Alzheimer’s is a condition where an individual gradually loses memory, and cognition, and suffers from many mental problems. The neurological disorder shrinks the affected person’s brain and its functions physically and literally and does not have a treatment for the person’s recovery. 

A big step forward 

Earlier studies did indicate that AD and gastrointestinal tract disorders were connected, but until this study came out, it was not clear what underpins their relationships: namely a genetic link.   

Shared pathways between AD and gastrointestinal disorders can help to design a therapy that can bypass conditions that go along with Alzheimer’s – such as hypertension, diabetes, obesity, depression, and fluctuating physical and mental activity. 

The drug challenge 

Most of the existing drug molecules either fail to cross the blood-brain barrier (BBB) or are `effluxed’ or resisted. As such, an effective therapy for Alzheimer’s disease or AD has eluded researchers due to the progressive nature of this disease. 

“The efficacy of existing drugs against Alzheimer’s disease is limited by their poor accessibility to the target area,” says Dr S.J.S. Flora, former Director, National Institute of Pharmaceutical Education and Research, Rae Bareli, Mohali.  

The Australian researchers found a common genetic variability and presence of certain genes at specific locations among individuals who had Alzheimer’s and other gastric disorders, like gastroesophageal reflux disease (GERD), peptic ulcer disease (PUD), gastritis-duodenitis, irritable bowel syndrome, and diverticulosis. They also found common pathways among these individuals.  

However, a common genetic variation was not found between AD and inflammatory bowel disease (IBD). 

The results of the study highlight the importance of the well-being of the brain and gut axis. The studies show that a brain and gut axis conveys the messages between the central nervous system and the gastrointestinal tract 

Microbiota & Vitamin B12 theories 

Microorganisms play an important role within the gut which regulates this communication. Disruptions in the gut microbiota can lead to diseases of the brain 

Another known mechanism is associated with a less than normal secretion of stomach acid that reduces the availability of Vitamin B12 and further increases the plasma homocysteine levels which can lead to dementia and memory loss.   

Dr Flora says, “Supplementation of Vitamin B12 has not given statistically relevant results on management of dementia.” This is because, in addition to gastrointestinal ones, there can be psychiatric, neurological, and haematological factors involved which cause dementia. 

Challenges to therapies 

However, no single research result can build the therapy. Certainly, there is a shared genetic architecture between AD and gastrointestinal disorders. But this information is not sufficient to manage AD 100 percent, as it involves many other factors and may require further research.    Therapeutics for various gastrointestinal conditions are available with proven success rates. Unfortunately, this is not true for AD.  

“Considering the multiplicity of gastrointestinal pathologies, treatment of both conditions with monotherapy (single drug treatment) seems unlikely,” says Dr Flora. The majority of gastrointestinal conditions can be contained locally and may not be a systemic factor such as a deficiency in Vitamin B12 or folate – which are believed to trigger AD.  

The gastritis factor 

No doubt, the latest genome study is an excellent comprehensive approach that has revealed the genetics behind the association between gastritis and Alzheimer’s. But it may require further research to understand the reasons or mechanism of AD because the study did not find that Alzheimer’s causes gastrointestinal disorders or vice-versa. 

Thus it is important to determine AD cases which are independent of gastritis. “Future studies must look at variables and manifestations of gastritis,” Dr Flora points out. 

Quick facts about Alzheimer’s Disease 

  • A slump in a person’s intellect is one of the most obvious and dominant signs of Alzheimer’s disease.
  • People in their 60s are more prone to this disorder where the function of their central nervous system continues to decline.
  • There is no cure for it and available medication works only to lessen the symptoms. The progressive nature of Alzheimer’s disease has made it a preeminent cause of death in the United States.
  • World Health Organization estimates that 50 million people are afflicted by dementia worldwide, of which Alzheimer’s is the most dominant affliction. Their number is projected to increase by 10 million every year. Larger studies have not been done for South Asian countries; among the Indian population, the number of people with dementia is expected to increase with the rising lifespans of the elderly.

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