Gut Inflammation May Be Another Piece of the Alzheimer's Puzzle

Researchers assembling the vast Alzheimer's puzzle may be nearing another important piece, as further evidence points to a connection between the gut and the brain.

Earlier animal research showed that Alzheimer's could be transmitted to young mice by transferring gut microbes, reinforcing the association between the digestive system and brain health.

Gut inflammation and Alzheimer's disease

A study published in 2023 provided additional evidence for the idea that inflammation may be the process behind this link.

"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 through two Alzheimer's prevention cohort studies.

At enrolment, participants completed several cognitive assessments, were interviewed about their family history, and were tested for a gene linked to a high risk of Alzheimer's.

A group of participants 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 patients, the increase was more marked in people with the amyloid plaques characteristic of Alzheimer's.

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

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

How the gut may affect the brain

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

Previous laboratory research has indicated that chemicals produced by gut bacteria can activate inflammatory signals in the brain. Other studies have also identified greater gut inflammation in patients with Alzheimer's than in control groups.

Heston and her colleagues believe that changes to the microbiome may prompt changes in the gut that produce inflammation throughout the body. Although mild, this inflammation may persist over time, causing small cumulative damage that ultimately affects the responsiveness of the body's 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 team is now studying mice to determine whether dietary changes linked to greater inflammation can induce the rodent equivalent of Alzheimer's.

After decades of investigation, there is still no effective treatment for the millions of people living with Alzheimer's around the world. However, scientists are moving closer, one piece at a time, as their understanding of its biological processes grows.

The research was published in Scientific Reports.

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