Identification of Microbiota within Aβ Plaque in APP/PS1 Transgenic Mouse

Microbes like viruses, bacteria, and fungi have all been reported in the brain of Alzheimer's postmortem patients and/or AD mouse model; however, the relationship between brain microbes and Aβ plaque deposition remains to be elucidated. In the present study, we first analyzed bacteria populations in the brain of 4-, 5-, and 6-month-old APP/PS1 mice and then examined the Aβ-positive loads of APP/PS1 mouse at 9 months old to identify bacteria in the brain by 16S rDNA sequencing. Finally, blood-brain barrier permeability was measured by injecting dextrans through the tail vein. Surprisingly, the diversity of microbial community gradually decreased in APP/PS1 mouse while wild-type mouse showed no obvious regularity. Moreover, Aβ-positive deposits in the brain showed a significantly higher relative abundance of microbiota than Aβ-negative tissues and age-matched wild-type mouse brain tissues. In addition, an increase in blood-brain barrier permeability was also observed in APP/PS1 mouse. The present study revealed the exact location of microbes within the Aβ plaques in the brain and suggested the potential antimicrobial effect of the Aβ peptide. We strongly recommend that future research on microbiota-related AD pathology should focus on the migration route of microbiota into the brain and how the microbiota enhance AD progression.