Periodontitis and Accelerated Brain Aging – Effects and Putative Mechanisms

• Applicants: Professor Dr. Hans Jörgen Grabe; Privatdozentin Dr. Birte Holtfreter
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology ; Biological Psychiatry ; Clinical Psychiatry, Psychotherapy, Child and Adolescent Psychiatry
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 573667931

The prevalence of neurodegenerative diseases, especially Alzheimer´s disease (AD), is increasing and there is substantial evidence that inflammatory processes are involved in their pathogenesis. Recently, evidence is accumulating that chronic inflammation of the periodontium (prevalence rates between 20 and 50%) is an independent risk factor for AD. We could demonstrate that AD-typical brain volume losses were significantly ameliorated longitudinally through treatment of periodontitis. There is evidence that a major pathogen of periodontitis, the gram-negative anaerobic bacterium P. gingivalis, can infect endothelia cells and enter the brain. In this application, we will test three models of how periodontitis may be involved in driving neurodegeneration: 1. The systemic bacterial translocation model; 2. The local bacterial translocation model (e.g. via the olfactory bulb); 3. The systemic inflammation model. Using epidemiological neuroimaging data and high-quality periodontitis measurements from the longitudinal Study of Health in Pomerania (SHIP, N≈3000) and from the German National Cohort (GNC, n≈12.000) we will firstly identify patterns of neurodegeneration of cortical and subcortical brain areas and the olfactory bulb tract pathways that are mostly affected by the burden of periodontitis. Secondly, we aim to disentangle the involvement of vascular brain lesions as a possible driver of atrophy of cortical and subcortical gray matter. Thirdly, we aim to clarify the role of periodontitis-associated pathogens, especially P. gingivalis, using oral microbiome data from gum pockets available in SHIP. Fourthly, the systemic inflammation model will be analyzed using inflammatory markers and cytokine panel data from SHIP. In all, we will potentially add important evidence to the impact of periodontitis, oral pathogens and systemic inflammation for brain aging and AD pathology.

• DFG Programme: Research Grants
• Co-Investigators: Stefan Frenzel; Dr. Christian Schwahn