Effect of early tooth loss on the mechanism of Alzheimer's disease pathogenesis.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K21102
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0907:Oral science and related fields
• Research Institution: Asahi University
• Principal Investigator: Ochi Suzuko 朝日大学, 歯学部, 助教 (70912591)
• Project Period (FY): 2021-08-30 – 2024-03-31
• Keywords: Alzheimer’s disease / tooth loss / amyloid-β / phosphorylated tau / microglia / astrocyte

Outline of Final Research Achievements

Alzheimer's disease (AD) is the most common neurodegenerative disease. Manycohort studies indicate that tooth loss is a risk factor for AD. The detailed mechanisms underlying the association between AD and tooth loss, however, are not yet fully understood. The purpose of this study is to analyze (1)stress status, (2)spatial cognitive performance, (3)amyloid population and neuroinflammation, (4)tau protein phosphorylation, and (5)synaptophysin formation in a third-generation mouse model of AD (AppNL-G-F KI mice) to clarify how early tooth loss affects the mechanism of AD development.
The results of this study indicated that early tooth loss is a chronic stressor. Chronic stress induced by early tooth loss activated the mobilization of microglia and astrocytes, increased the secretion of inflammatory cytokines, and exacerbated neuroinflammation, Aβ deposition, and phosphorylated tau protein, causing synaptic dysfunction and spatial learning deficits in AD model mice.

Free Research Field

歯の早期喪失

Academic Significance and Societal Importance of the Research Achievements

超高齢社会である日本においてはもちろん、世界的にも認知症患者の人口の増加は大きな社会問題になっている。特にADは認知症患者の約7割を占める。ADは多因子疾患であり発症を予防するためにも発症の危険因子を把握するとともに改善することが大切である。
本研究では、第三世代ADモデルマウス（AppNL-G-F KIマウス）を用いて、歯の早期喪失がADの発症メカニズムに及ぼす影響を検討することにより、ADと歯の喪失が密接に関与することが明らかにできると考えられる。研究が達成されることにより、口腔健康が全身の疾患予防に重要であることが再認識され、学問的にもより注目され得るきっかけになると考えられる。