Elucidation of Alzheimer's disease exacerbation mechanism of periodontitis centering on microglia-related neuroinflammation

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K11478
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional basic dentistry
• Research Institution: Kyushu University
• Principal Investigator: Take Hiro 九州大学, 歯学研究院, 准教授 (10420598)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 歯周病 / ミクログリア / アルツハイマー病

Outline of Final Research Achievements

In this study, we have found that systemically exposure of PgLPS, a component of periodontitis Porphyromonas gingivalis (Pg) induces the Alzheimer-disease (AD) -like phenotypes, including learning and memory decrease, microglia-dependent neuroinflammation and hippocampal intraneuronal amyloid A beta accumulation were induced in the wild-type middle-aged mice. It was revealed that AD-like phenotypes did not induced in middle-aged cathepsin (Cat) B deficient mice after exposure PgLPS, therefore it is considered that CatB is a causative enzyme for PgLPS-induced AD-like pathology. On the other hand, spleen hypertrophy associated with a significant increase in dendritic cells and Th17 cells observed in the spleen of wild-type mice after systemically exposure of PgLPS, however the phenotypes in spleen was not observed in mice deficient in CatS deficient mice, thus indicates that CatS may as a causative enzyme of PgLPS induced systemic inflammatory amplification.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

本研究成果は口腔ケアの認知症予防における重要性を広く発信するに加え、CatBならびにCatSの特異的阻害剤は認知症の発症ならびに進行を阻む可能性が示され、今後の展開が期待される。