Elucidation of the mechanism of periodontal disease involved in the progression of Alzheimer's disease

2017 Fiscal Year Final Research Report

• Project/Area Number: 26293438
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Periodontology
• Research Institution: National Center for Geriatrics and Gerontology
• Principal Investigator: MATSUSHITA Kenji 国立研究開発法人国立長寿医療研究センター, 口腔疾患研究部, 部長 (90253898)
• Co-Investigator(Kenkyū-buntansha): 多田 浩之 東北大学, 歯学研究科, 講師 (70431632) ; 萩原 真 国立研究開発法人国立長寿医療研究センター, 口腔疾患研究部, 流動研究員 (30546099)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 認知症 / 歯周病 / 歯周病原細菌 / 神経炎症 / アミロイドβ / ミクログリア / 血液脳関門 / Porhyromonas gingivalis

Outline of Final Research Achievements

We investigated by using a transgenic mouse model of AD whether periodontitis evoked by P. gingivalis modulates the pathological features of AD. Cognitive function was significantly impaired in periodontitis-induced APP-Tg mice, compared to that in control APP-Tg mice. Levels of Amiloid β (Aβ) deposition, Aβ40, and Aβ42 in both the hippocampus and cortex were higher in inoculated APP-Tg mice than in control APP-Tg mice. Furthermore, levels of IL-1β and TNF-α in the brain were higher in inoculated mice than in control mice. The levels of LPS were increased in the serum and brain of P.gingivalis-inoculated mice. P. gingivalis LPS induced production of Aβ40 and Aβ42 in neural cell cultures and strongly enhanced TNF-α and IL-1β production in a culture of microglial cells primed with Aβ. Periodontitis evoked by P.gingivalis may exacerbate brain Aβ deposition, leading to enhanced cognitive impairments, by a mechanism that involves triggering brain inflammation.

Free Research Field

歯周病学、老年歯学、口腔細菌学、口腔免疫学