Alzheimer's disease-like pathology induced by in middle-aged mice is mediated by NLRP3 inflammasome via the microbiota-gut-brain axis.

BACKGROUND

() has been found to enter the brain and induce inflammation, contributing to Alzheimer's disease (AD). is also closely linked to gut dysbiosis. However, does induce AD-like pathology through the microbiota-gut-brain axis? There is limited literature on this topic.

OBJECTIVE

To determine the precise causal link among , intestinal inflammation, and AD-related pathology.

METHODS

12- to 13-month-old female C57BL/6J mice were subjected to ligature placement and oral administration of over a 24-week period. Then, cognitive performance was evaluated with behavioral tests, while AD neuropathological changes, neuroinflammation, and intestinal inflammation were assessed through qPCR, immunofluorescence, and western blot, and gut microbiota was analyzed by 16S rRNA.

RESULTS

Mice exposed to showed impaired behavior in open field test, novel object recognition, and Y-maze tests. The bacterium infiltrated their brains, increasing Aβ, AβPP, and Aβ fragments, promoting tau phosphorylation and microglial activation, and reducing levels of ZO-1, PSD95, SYP, and NeuN proteins. Inflammatory factors like NLRP3, caspase-1, IL-1β, IL-6, and TNF-α were elevated in both brains and intestine, while ZO-1 and occludin levels decreased in intestine. also altered gut microbial compositions.

CONCLUSIONS

induced gut dysbiosis and activated the NLRP3 inflammasome in the intestine and brains of mice. This led to impairment of both the intestinal and brain-blood barriers, triggering neuroinflammation and promoting the progression of AD. These findings highlight the critical role of NLRP3 inflammasome activation in the microbiota-gut-brain axis in the AD-like pathology induced by