Chronic oral application of a periodontal pathogen results in brain inflammation, neurodegeneration and amyloid beta production in wild type mice.
Level 5 - mechanism / opinion, no new human data
Animal research
PubMed 30281647 · doi:10.1371/journal.pone.0204941
What was done
Researchers evaluated whether chronic oral exposure to the periodontal pathogen Porphyromonas gingivalis (Pg) induces Alzheimer-like neuropathology in non-transgenic mice. Ten 8-week-old wild-type C57BL/6 mice received repeated oral administration of Pg/gingipain three times per week for 22 weeks, while ten control mice received vehicle alone. Hippocampal brain tissues were analyzed using immunofluorescence, confocal microscopy, and RT-qPCR for bacterial translocation, inflammatory cytokines (TNFα, IL1β, IL6), glial activation, neuronal loss (NeuN, Fluoro Jade C), amyloid-related gene expression and deposition (Aβ42, APP, BACE1, ADAM10, PSEN1), and tau phosphorylation (phospho-Tau Ser396).
What was found
Pg and gingipain translocated to the hippocampus in treated mice. Compared to controls, Pg-exposed mice showed: - Increased inflammatory cytokines: IL6 (p < 0.01), TNFα (p < 0.00001), and IL1β (p < 0.00001). - Increased microgliosis (p < 0.01) and astrogliosis (p < 0.0001). - Evident neurodegeneration via decreased NeuN positivity/rbFox3 expression and increased Fluoro Jade C-positive neurons. - Altered amyloid-related gene expression: increased APP (p < 0.05) and BACE1 (p < 0.001), decreased ADAM10 (p < 0.01), and non-significantly increased PSEN1 (p = 0.07). - Extracellular Aβ42 deposition (p < 0.00001) and phospho-Tau (Ser396) formation of neurofibrillary tangles (p < 0.00001), which were not present in vehicle controls.
Why it matters
This study demonstrates that chronic oral infection with a common periodontal bacterium can translocate to the brain and initiate neurodegenerative changes, amyloid plaque formation, and neurofibrillary tangles in standard wild-type mice without genetic modification.
Limits
The study was conducted in a small sample of mice (10 per group), limiting direct translation to human Alzheimer's disease pathology and progression. The abstract does not report behavioral or cognitive functional testing.
Cited by
- supports Porphyromonas gingivalis secretes chemicals that cleave and activate beta-amyloid and induce tau protein phosphorylation in laboratory models.