IADR Abstract Archives
Oral Pathogen-Induced Chronic Inflammation Promotes Development of Alzheimer’s Disease
Objectives: Recent studies suggest that chronic systemic inflammation might play a role in the pathogenesis of Alzheimer’s disease (AD), and that periodontitis, one of the most prevalent inflammatory diseases, may be involved in the development and progression of AD. However, few studies have investigated whether the development of AD is related to specific pathogen-induced inflammation or to the degree of severity of inflammation.
Methods: Using wild type C57BL/6J male and female mice, we subcutaneously implanted osmotic pumps to continuously deliver LPS derived from P.gingivalis, a key pathogen in chronic periodontitis, or LPS derived from E.coli, the most common GI tract pathogen, for 4 weeks at 250 µg/kg/day (low dose) or 500 µg/kg/day (high dose). After three weeks of LPS administration, spatial learning and memory of mice were assessed by Morris Water Maze (MWM). After four weeks of LPS delivery, the proinflammatory cytokines, IL-1β and TNF-α, were measured by ELISA.
Results: A sustained exposure to high dose P.g-LPS or E.coli-LPS significantly impaired spatial learning and memory in the mice, with P.g-LPS having a more prominent effect. In contrast, a low dose exposure did not cause impairment. The levels of brain proinflammatory cytokines, IL-1β and TNF-α, were significantly elevated after exposure to high dose P.g-LPS or E.coli-LPS. With low dose exposure, a significant increase in brain IL-1β levels was only observed with P.g-LPS and not E.coli-LPS.
Conclusions: Our results suggest that moderate or severe systemic inflammation can cause neuroinflammation and impair cognitive function, which is consistent with previous clinical findings that severe periodontal disease doubles the risk of AD onset. An interesting observation from our study is that, compared to the GI pathogen E.coli, the oral pathogen P.gingivalis may be a more specific inducer of neuroinflammation and cognitive dysfunction; however, this requires further investigation.
Methods: Using wild type C57BL/6J male and female mice, we subcutaneously implanted osmotic pumps to continuously deliver LPS derived from P.gingivalis, a key pathogen in chronic periodontitis, or LPS derived from E.coli, the most common GI tract pathogen, for 4 weeks at 250 µg/kg/day (low dose) or 500 µg/kg/day (high dose). After three weeks of LPS administration, spatial learning and memory of mice were assessed by Morris Water Maze (MWM). After four weeks of LPS delivery, the proinflammatory cytokines, IL-1β and TNF-α, were measured by ELISA.
Results: A sustained exposure to high dose P.g-LPS or E.coli-LPS significantly impaired spatial learning and memory in the mice, with P.g-LPS having a more prominent effect. In contrast, a low dose exposure did not cause impairment. The levels of brain proinflammatory cytokines, IL-1β and TNF-α, were significantly elevated after exposure to high dose P.g-LPS or E.coli-LPS. With low dose exposure, a significant increase in brain IL-1β levels was only observed with P.g-LPS and not E.coli-LPS.
Conclusions: Our results suggest that moderate or severe systemic inflammation can cause neuroinflammation and impair cognitive function, which is consistent with previous clinical findings that severe periodontal disease doubles the risk of AD onset. An interesting observation from our study is that, compared to the GI pathogen E.coli, the oral pathogen P.gingivalis may be a more specific inducer of neuroinflammation and cognitive dysfunction; however, this requires further investigation.