(1) Oral Pathogen-Induced Chronic Inflammation May Promote the Development of Alzheimer’s Disease

Introduction: Recent studies propose an involvement of chronic inflammation in the pathogenesis of Alzheimer’s disease (AD), and it has been suggested that periodontitis may be involved in the development and progression of AD. However, few studies have investigated whether the development of AD is related to specific pathogens or to the severity of the inflammation that they induce.

Methods: We investigated the effect of Oral-vs-GI pathogen-induced peripheral chronic inflammation on the development of AD using C57 wild type mice. LPS derived from P. gingivalis or LPS derived from E.coli was continuously delivered for 4 weeks at 250 µg/kg/day (low-dose) or 500 µg/kg/day (high-dose). After three weeks of LPS administration, the 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: We found that a sustained exposure to high-dose P.g-LPS or E.coli-LPS significantly impaired cognition and increased IL-1β and TNF-α in brain tissue lysate. In contrast, a low-dose exposure did not cause cognitive impairment in any groups, and an increase in brain IL-1β levels was only observed with low-dose P.g-LPS and not E.coli-LPS.

Conclusions: Our results suggest that moderate-to-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.

Lead Author’s Contributions to the Research Project: The Lead Author was responsible for experiment design, data collection, performing data analysis, and the composition of the abstract.