Scientists investigating the complex puzzle of Alzheimer’s disease have made progress in understanding the link between our gut and brain. Recent animal studies have shown that gut microbes can be passed from older mice to younger ones, leading to the development of Alzheimer’s. This confirms the connection between the digestive system and brain health. Another study has provided further evidence that inflammation could be the mechanism behind this process.
“We showed 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,” says University of Wisconsin psychologist Barbara Bendlin.
A team of researchers led by Margo Heston, a pathologist from the University of Wisconsin, conducted a study to investigate the relationship between fecal calprotectin, inflammation, and Alzheimer’s disease. They recruited 125 individuals from two Alzheimer’s prevention cohort studies and tested their stool samples for fecal calprotectin.
The participants underwent cognitive tests, interviews on family history, and tests for a high-risk Alzheimer’s gene. A subset of them also underwent clinical tests for signs of amyloid protein clumps, which are a common indication that pathology responsible for the neurodegenerative condition was underway.
The results showed that levels of calprotectin were generally higher in older patients, and even more pronounced in those with Alzheimer’s characteristic amyloid plaques. The levels of other Alzheimer’s disease biomarkers also increased with levels of inflammation, and memory test scores dropped with higher calprotectin as well.
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Surprisingly, even the participants without a diagnosis of Alzheimer’s had poorer memory scores with higher levels of calprotectin.
“We can’t infer causality from this study; for that, we need to do animal studies,” cautions Heston.
According to a laboratory analysis, chemicals produced by gut bacteria can activate inflammatory signals in our brains. Moreover, numerous studies have observed higher levels of gut inflammation in patients with Alzheimer’s compared to healthy individuals.
Researchers led by Heston believe that a change in the microbiome triggers changes in the gut, which leads to chronic, mild inflammation. This inflammation gradually causes damage to our body’s barriers, eventually affecting their sensitivity.
“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,” says University of Wisconsin bacteriologist Federico Rey.
The researchers are currently conducting experiments on mice to determine whether dietary modifications that lead to increased inflammation can activate the rodent model of Alzheimer’s. Despite decades of research, there is still no effective treatment available for the millions of people worldwide who are suffering from Alzheimer’s. However, with an improved understanding of the underlying biological mechanisms, scientists are slowly but surely making progress towards finding a cure.
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References:
1. Heston, M.B., Hanslik, K.L., Zarbock, K.R. et al. Gut inflammation associated with age and Alzheimer’s disease pathology: a human cohort study. Sci Rep 13, 18924 (2023). https://doi.org/10.1038/s41598-023-45929-z
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