Alzheimer’s disease as a co-morbidity of chronic periodontitis with Porphyromonas gingivalis as a causative link between both diseases

A numerous clinical and epidemiological studies show an association between chronic periodontitis 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. In this proposal we seek to examine in detail the comorbidity between PD and AD with special emphasis on the P.g role in the pathogenesis of AD. To this end we will: i) establish a novel, highly sensitive assay allowing for identification of the presence of P.g and/ or its virulence factors in the CNS; ii) identify virulence factors essential for P.g-induced neurodegenerative changes in wild-type mice and different murine models of AD and establish a reliable model for discovery of novel biomarkers;; iii) 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; v) employ animal models to provide a proof of concept that oral infection with P.g (experimental PD) impacts (induces and/or accelerates and/or exasperates) AD; vi) use novel, periodontal pathogen-specific antibacterial compounds targeting P.g glutaminyl cyclase (pQC) in the innovative approach to interfere with the assembly of virulence factors and test if they can affect AD development and progression. By casting new light on mechanisms driving comorbidity of PD in AD the completion of the project will pave the way to novel early diagnostic, preventive, therapeutic and monitoring strategies needed for successful management of AD

A numerous clinical and epidemiological studies show an association between chronic periodontitis 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. In this proposal we seek to examine in detail the comorbidity between PD and AD with special emphasis on the P.g role in the pathogenesis of AD. To this end we will: i) establish a novel, highly sensitive assay allowing for identification of the presence of P.g and/ or its virulence factors in the CNS; ii) identify virulence factors essential for P.g-induced neurodegenerative changes in wild-type mice and different murine models of AD and establish a reliable model for discovery of novel biomarkers;; iii) 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; v) employ animal models to provide a proof of concept that oral infection with P.g (experimental PD) impacts (induces and/or accelerates and/or exasperates) AD; vi) use novel, periodontal pathogen-specific antibacterial compounds targeting P.g glutaminyl cyclase (pQC) in the innovative approach to interfere with the assembly of virulence factors and test if they can affect AD development and progression. By casting new light on mechanisms driving comorbidity of PD in AD the completion of the project will pave the way to novel early diagnostic, preventive, therapeutic and monitoring strategies needed for successful management of AD.