Elucidation of the mechanism of periodontal disease involved in the progression of Alzheimer's disease
| Project/Area Number |
26293438
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Periodontology
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| Research Institution | National Center for Geriatrics and Gerontology |
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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)
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| 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)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000)
Fiscal Year 2016: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2014: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| 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 / アルツハイマー病 / Porphyromonas gingivalis / 酸化ストレス / 慢性炎症 / 生活習慣病 / 因果関係 / 歯周病関連細菌 |
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| 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.
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Report
(4 results)
Research Products
(72 results)
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[Journal Article] Periodontitis induced by bacterial infection exacerbates features of Alzheimer's disease in transgenic mice.2017
Author(s)
Ishida N, Ishihara Y, Ishida K, Tada H, Funaki-Kato Y, Hagiwara M, Ferdous T, Abdullah M, Mitani A, Michikawa M, Matsushita K.
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Journal Title
NPJ Aging Mech Dis.
Volume: 3
Pages: 15-15
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Vinculin and Rab5 complex is requited for uptake of Staphyrococcus aureus and interleukin-6 expression.2014
Author(s)
Hagiwara M, Kokubu E, Sugiura S, Komatsu T, Tada H, Isoda R, Tanigawa N, Kato Y, Ishida N, Kobayashi K, Nakashima M, Ishihara K, Matsushita K.
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Journal Title
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Book] In Innovative Research on Biosis-Abiosis Intelligent Interface 2014 (Sasaki K, Suzuki O, and Takahashi N eds).2015
Author(s)
Ishida N, Ishihara Y, Ishida K, Tada H, Kato Y, Isoda R, Hagiwara M, Michikawa M, Noguchi T, and Matsushita K
Total Pages
7
Publisher
Springer Japan
Related Report
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[Book] Chapter 26. Periodontal disease as a possible risk factor for Alzheimer’s disease, in Innovative Research on Biosis-Abiosis Intelligent Interface 20142015
Author(s)
Ishida N, Ishihara Y, Ishida K, Tada H, Kato Y, Isoda R, Hagiwara M, Michikawa M, Noguchi T, and Matsushita K
Total Pages
8
Publisher
Springer Japan
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