A study published on Nature.com earlier this month has added further support to the theory that inflammation, stemming from within the gut biome, could be the base cause of Alzheimer’s disease. The study investigates the relationship between gut inflammation, ageing, and Alzheimer’s disease (AD) pathology.
“We showed people with Alzheimer’s disease have more gut inflammation,” University of Wisconsin psychologist Barbara Bendlin said, “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.”
The study explored the concept of “inflammaging,” where chronic low-grade inflammation may play a role in age-related diseases, possibly mediated by gut microbes impacting intestinal barrier integrity. The research aimed to determine if increased gut inflammation was associated with advanced age and AD pathology.
Researchers assessed faecal samples from older adults to measure calprotectin, a marker of intestinal inflammation. They used multiple regression analysis to examine the relationships between faecal calprotectin levels, clinical diagnosis, participant age, AD pathology biomarkers, amyloid burden measured via PiB PET imaging, and cognitive test performance measuring executive function and verbal learning/recall.
The findings indicated that calprotectin levels were elevated in advanced age and higher in participants diagnosed with amyloid-confirmed AD dementia. Moreover, higher calprotectin levels were associated with greater amyloid burden in individuals with AD dementia, suggesting a connection between intestinal inflammation, brain pathology, and AD progression.
The study proposes that age-related changes in the gut microbiome could lead to intestinal inflammation and barrier degradation, allowing bacterial components to enter systemic circulation and trigger inflammation. Evidence supports increased gut permeability with ageing and age-related diseases, potentially contributing to systemic inflammation.
Although few studies have explored elevated inflammation and permeability in healthy ageing adults, the link between gut dysbiosis, peripheral inflammation, and AD is becoming clearer, with implications for AD pathogenesis.
The study measured fecal calprotectin in middle-aged and older adults across the AD continuum to understand the role of intestinal inflammation in ageing and as a precursor to AD pathology. Results showed associations between faecal calprotectin levels, age, cognitive function, and AD pathology markers.
Notably, calprotectin levels were higher in participants with amyloid-confirmed AD dementia, increased with age, and were correlated with amyloid burden in individuals with AD.
In cognitively unimpaired participants, calprotectin levels were associated with subtle cognitive changes linked to future AD onset, highlighting a potential early indicator of AD-related cognitive decline.
In conclusion, the findings suggest that aging coincides with intestinal inflammation, observed in AD cases with amyloid positivity and possibly exacerbating amyloid accumulation. The study implies that targeting intestinal inflammation and potential permeability could be modifiable factors in mitigating age-related changes and AD development.
