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

Acronym	Gums&Brain (Reference Number: JPND2019-466-285)
Project Topic	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 (Pg) 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 CP and AD with special emphasis on the Pg 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 Pg and/or its virulence factors in the CNS; ii) identify virulence factors essential for Pg-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 Pg (experimental CP) impacts (induces and/or accelerates and/or exasperates) AD; vi) use novel, periodontal pathogen-specific antibacterial compounds targeting Pg 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.
Network	JPCOFUND2
Call	PERSONALISED MEDICINE FOR NEURODEGENERATIVE DISEASES

Project partner

Number	Name	Role	Country
1	Jagiellonian University	Coordinator	Poland
2	Fraunhofer Institut für Zelltherapie und Immunologie Leipzig	Partner	Germany
3	Aarhus University	Partner	Denmark
4	Czech Academy of Science	Partner	Czech Republic
5	University of Bergen	Partner	Norway