A numerous clinical and epidemiological studies show an association between chronic periodontitis (PD) and Alzheimer’s disease (AD). AD, the most common form of dementia, is manifested with neuroinflammation consistent with microbiological infection, including microglial activation, inflammasome and complement activation as well as altered cytokine profiles. Infectious agents, including periodontal pathogen Porphyromonas gingivalis (P.g) were identified in the AD patient brains and postulated to be an etiologic factor but causation is still very poorly investigated. The general aim of the project is to examine in detail the comorbidity between PD and AD with special emphasis on the P.g role in the pathogenesis of AD.

 

Specific aims of the project:

• establish a novel, highly sensitive assay allowing for identification of the presence of P.g and/or its virulence factors in the CNS

• identify virulence factors essential for P.g-induced neurodegenerative changes in wild-type mice and different murine models of AD 

• evaluate the impact of eradication of specific periodontal pathogens on the level of inflammatory markers known to be associated with severity and/or progression of AD

• employ animal models to provide a proof of concept that oral infection with P.g (experimental PD) impacts (induces and/or accelerates) AD

• use novel, periodontal pathogen-specific antibacterial compounds targeting P.g glutaminyl cyclase (pgQC) in the innovative approach to interfere with the assembly of virulence factors and test if they can affect AD development and progression.