Porphyromonas gingivalis Impairs Microglial Aβ Clearance in a Mouse Model

Area of Science:

• Neuroscience
• Microbiology
• Pathology

Background:

• Porphyromonas gingivalis (Pg) is linked to Alzheimer's disease (AD) and promotes amyloid-beta (Aβ) accumulation.
• The mechanism by which Pg affects Aβ clearance in the brain is not fully understood.

Purpose of the Study:

• To investigate the impact of Pg infection on microglial Aβ clearance and cognitive function in a mouse model of AD.
• To elucidate the role of gingipains in Pg-mediated impairment of Aβ clearance.

Main Methods:

• APP/PS1 mice were infected with three different strains of Pg.
• In vitro experiments assessed microglial Aβ internalization and phagocytosis.
• The effect of gingipain inhibitors on Aβ clearance and cognitive function was evaluated.

Main Results:

• Pg infection in APP/PS1 mice led to reduced microglial Aβ internalization, increased brain Aβ deposition, and cognitive deficits.
• Pg inhibited microglial Aβ clearance by hydrolyzing CD14 via gingipains, disrupting the Vav-Rac/Cdc42 signaling pathway.
• Gingipain inhibition reversed these effects, restoring Aβ clearance and improving cognitive function.

Conclusions:

• Pg infection exacerbates AD pathology by impairing microglial Aβ clearance through gingipain-mediated mechanisms.
• Gingipain inhibitors show therapeutic potential for treating Porphyromonas gingivalis-associated Alzheimer's disease.