Research shows gut inflammation associated with aging and Alzheimer’s

A new study by researchers at the University of Wisconsin School of Medicine and Public Health has linked inflammation in the gut to the amyloid plaques that build up in the brains of Alzheimer’s sufferers.

Longevity.Technology: The research, which was published in the Nature journal Scientific Reports, showed that as levels of inflammatory marker calprotectin increased, so too did the amount of amyloid plaque accumulation. As well as these results, found by testing the stool samples of volunteer participants, the researchers also found that the levels of Alzheimer’s disease biomarkers in cerebrospinal fluid (CNS) also increased. These increasing levels coincided with worsening scores in tests evaluating the volunteers’ verbal memory function [1].

The researchers found that even volunteers who did not have Alzheimer’s disease still had lower scores on a memory test correlated with higher levels of calprotectin.

“We showed [that] people with Alzheimer’s disease have more gut inflammation, 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,” explained Barbara Bendlin, professor of medicine, UW School of Medicine and Public Health, and senior author on the paper [2].

Previous research has determined that calprotectin levels rise with older age, and this was also found in this study. One theory suggests that inflammation in the gut is caused by changes in the microbiome that occur as people age and this inflammation can further contribute to neurodegenerative diseases. 

When we spoke to Longevity Center’s Dr Anna Modelska-Ziółkiewicz earlier this week, she explained that the gut is central to our overall well-being, being responsible for absorbing nutrients and synthesizing key vitamins and neurotransmitters.

“A balanced gut microbiome helps to regulate our immune system and reduce inflammation, which is involved in many age-related conditions,” she said, adding that research has suggested links between gut microbiome imbalances and neurological conditions, such as depression, anxiety and Alzheimer’s disease.

Additional research is warranted to illuminate the relationship between inflammation and Alzheimer’s, and to understand whether there is a cause-and-effect link. “We can’t infer causality from this study; for that, we need to do animal studies,” Bendlin explained.

Bendlin’s two collaborators and senior authors on this paper, Federico Rey, associate professor of bacteriology, UW–Madison, and Tyler Ulland, assistant professor of pathology and laboratory medicine, UW School of Medicine and Public Health, are now undertaking animal studies to determine whether inflammation or diet changes can elicit a murine version of Alzheimer’s in a mouse model.

In an earlier study, the research team found significant differences between the gut microbiome of people with Alzheimer’s and the microbiome of those without it [3]. The paper suggested that gut changes may contribute to systemic inflammation that disrupts the blood-brain barrier, which normally protects the brain from infection and toxins, according to Rey.

“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,” he said [2].

By making precise changes in the gut microbiome, Rey and Ulland’s labs plan to alter gut permeability in a mouse model of Alzheimer’s disease and test these ideas.

The idea that the gut and brain are functionally connected has been gaining ground over the last decade, and this study adds grist to mill, contributing evidence that asymptomatic gut inflammation and Alzheimer’s disease may be linked.

“This study, although not definitive, provides additional evidence that changes in gut health could be linked to Alzheimer’s pathology,” Ulland explains. “It is therefore very important to continue to study the link between changes in the gut, such as inflammation or increased gut permeability, and Alzheimer’s disease onset and progression [2].”

The researchers are now working with study volunteers using a ‘gold standard test’ for leaky gut that measures how certain sugars are excreted in urine. Another Wisconsin Alzheimer’s Disease Research Center clinical study will test whether taking probiotics helps improve gut inflammation to assess whether they could possibly prevent cognitive decline caused by Alzheimer’s disease and related dementias.

READ MORE: The gut microbiome – a key to unlocking healthy aging

[1] https://www.nature.com/articles/s41598-023-45929-z
[2] https://bit.ly/49aKbhz
[3] https://www.nature.com/articles/s41598-017-13601-y