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

作者:Cao, Jianing; Wang, Min; Gong, Congcong; Amakye, William Kwame; Sun, Xiaoyu; Ren, Jiaoyan*
来源:Journal of Molecular Neuroscience, 2021, 71(5): 953-962.
DOI:10.1007/s12031-020-01715-4

摘要

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 A beta 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 A beta-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, A beta-positive deposits in the brain showed a significantly higher relative abundance of microbiota than A beta-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 A beta plaques in the brain and suggested the potential antimicrobial effect of the A beta 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.