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Mahmoud Elashiry1, Angelica Carroll1, Jessie Yuan1

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Porphyromonas gingivalis-infected exosomes from the mouth can cross the blood-brain barrier. These microbial exosomes may contribute to Alzheimer's disease pathogenesis by reaching the brain.

Keywords:
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Area of Science:

  • Microbiology
  • Neuroscience
  • Immunology

Background:

  • Porphyromonas gingivalis (Pg) and its proteases are linked to Alzheimer's disease (AD) pathogenesis.
  • Exosomes (EXO), secreted vesicles, increase with aging and senescence.
  • Previous work showed Pg-infected cell EXO transmit senescence and cause bone loss.

Purpose of the Study:

  • To investigate if exosomes from periodontitis (PD) can cross the blood-brain barrier (BBB).
  • To determine the origin and brain-penetrating ability of microbial-induced exosomes.
  • To explore the potential role of these exosomes in AD.

Main Methods:

  • Induced periodontitis in mice via Pg oral gavage.
  • Isolated and characterized exosomes (EXO) from gingiva and brain tissues.
  • Tracked labeled EXO biodistribution in recipient mice brains using in vivo imaging and microscopy.
  • Assessed human PD EXO effects on BBB integrity and permeability in vitro.

Main Results:

  • Pg antigens were detected in EXO from gingival and brain tissues of infected mice.
  • Gingival PD EXO injected into mice successfully penetrated recipient brains and localized to microglial cells.
  • Human PD EXO, containing IL-1β and IL-6, increased BBB permeability in vitro.

Conclusions:

  • Microbial-induced exosomes from the oral cavity can disseminate systemically.
  • These exosomes are capable of crossing the blood-brain barrier.
  • This provides a novel mechanism linking oral pathogens to neuroinflammation and potential AD pathogenesis.