Gut Inflammation May Offer Another Clue to Alzheimer’s

Alzheimer’s, gut inflammation and amyloid plaques

Researchers working to assemble the vast Alzheimer’s puzzle may be nearing another key piece, after finding a further connection between the gut and the brain.

Studies in animals have already shown that Alzheimer’s can be transmitted to young mice by transferring gut microbes, supporting a relationship between the digestive system and brain health.

Research published in 2023 provides additional evidence for the idea that inflammation may be the process behind this connection.

"We showed people with Alzheimer's disease have more gut inflammation," University of Wisconsin psychologist Barbara Bendlin said when the research was published, "and among people with Alzheimer's, when we looked at brain imaging, those with higher gut inflammation had higher levels of amyloid plaque accumulation in their brains."

University of Wisconsin pathologist Margo Heston and an international research team measured faecal calprotectin - an inflammation marker - in stool samples from 125 people enrolled in two Alzheimer’s prevention cohort studies.

At enrolment, participants completed several cognitive assessments, alongside family-history interviews and testing for a gene associated with high Alzheimer’s risk.

A subgroup also underwent clinical testing for evidence of amyloid protein clumps, a frequent sign that the pathology underlying this neurodegenerative condition had begun.

Although calprotectin concentrations tended to be higher among older participants, the increase was still more marked in people with amyloid plaques characteristic of Alzheimer’s.

Other biomarkers of Alzheimer’s disease likewise rose alongside inflammation levels, while memory-test results declined as calprotectin increased.

Higher calprotectin was also associated with worse memory scores in participants who had not been diagnosed with Alzheimer’s.

How gut inflammation may affect the brain

"We can't infer causality from this study; for that, we need to do animal studies," cautioned Heston.

Earlier laboratory work found that chemicals produced by gut bacteria can activate inflammatory signals in the brain. In addition, other research has identified greater gut inflammation in patients with Alzheimer’s than in control groups.

Heston and her colleagues believe changes to the microbiome may set off alterations in the gut that produce inflammation throughout the body. Although mild, this inflammation is persistent, producing subtle cumulative harm that may ultimately disrupt the sensitivity of the body’s protective barriers.

"Increased gut permeability could result in higher blood levels of inflammatory molecules and toxins derived from gut lumen, leading to systemic inflammation, which in turn may impair the blood-brain barrier and may promote neuroinflammation, and potentially neural injury and neurodegeneration," said University of Wisconsin bacteriologist Federico Rey.

Testing diet-related inflammation in mice

The researchers are now studying mice to determine whether dietary changes linked to increased inflammation can induce the rodent form of Alzheimer’s.

After decades of investigation, no effective treatment is yet available for the millions of people living with Alzheimer’s around the world. However, scientists are moving closer step by step as their understanding of the biological processes improves.

The research was published in Scientific Reports.

An earlier version of this article was published in January 2024.