Fight Aging!

There is some debate over the degree to which periodontal disease contributes to neurodegenerative conditions. A mechanism to link the two exists: gum disease produces chronic inflammation, allowing bacteria and bacterial products into the bloodstream to provoke the immune system. Chronic inflammation in brain tissue is a feature of neurodegenerative conditions, and inflammation elsewhere in the body tends to generate matching inflammatory behavior in the immune cell populations of the brain. Thus one would expect the brain to fare less well over time given the presence of gum disease. Epidemiology, however, suggests that the effect size here is small, only a few percentage points of greater risk of dementia resulting from gum disease.

In today's research materials, researchers report that oral bacteria associated with periodontal disease can travel to the brain, and there provoke microglia, innate immune cells of the central nervous system, into greater activation. This in turn can accelerate the progression of age-related neurodegeneration leading to Alzheimer's disease and other conditions. Numerous research groups have produced evidence to show that greater inflammatory behavior in microglia is associated with neurodegenerative conditions, and appears to drive the progression of pathology. But is the contribution of periodontal disease to this overactivation of microglia characteristic of later life large or small? The answer to that question remains to be settled.

Gum disease linked to buildup of Alzheimer's plaque formation

In a new paper, researchers demonstrate that gum disease can lead to changes in brain cells called microglial cells, which are responsible for defending the brain from amyloid plaque. This plaque is a type of protein that is associated with cell death, and cognitive decline in people with Alzheimer's. The study provides important insight into how oral bacteria makes its way to the brain, and the role of neuroinflammation in Alzheimer's disease. Using mouse oral bacteria to cause gum disease in lab mice, the scientists were able to track periodontal disease progression in mice and confirm that the bacteria had traveled to the brain. They then isolated the brain microglial cells and exposed them to the oral bacteria. This exposure stimulated the microglial cells, activated neuroinflammation, and changed how microglial cells dealt with amyloid plaques.

Microglial cell response to experimental periodontal disease

Microglial activation is critical for modulating the neuroinflammatory process and the pathological progression of neurodegenerative diseases, such as Alzheimer's disease (AD). Microglia are involved in forming barriers around extracellular neuritic plaques and the phagocytosis of β-amyloid peptide (Aβ). In this study, we tested the hypothesis that periodontal disease (PD) as a source of infection alters inflammatory activation and Aβ phagocytosis by the microglial cells.

Experimental PD was induced using ligatures in C57BL/6 mice for 1, 10, 20, and 30 days to assess the progression of PD. Animals without ligatures were used as controls. Ligature placement caused progressive periodontal disease and bone resorption that was already significant on day 1 post-ligation and continued to increase until day 30. The severity of periodontal disease increased the frequency of activated microglia in the brains on day 30 by 36%. In parallel, heat-inactivated PD-associated total bacteria and Klebsiella variicola increased the expression of TNFα, IL-1β, IL-6, TLR2, and TLR9 in microglial cells in vitro. Incubation of microglia with Klebsiella variicola increased the Aβ-phagocytosis by 394% and the expression of the phagocytic receptor MSR1 by 33-fold compared to the non-activated cells. These results support a direct role of PD-associated pathogens in neuroinflammation.