Early-life stress induces the development of Alzheimer's disease pathology via angiopathy
| Project/Area Number |
17K16408
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Psychiatric science
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| Research Institution | Tokyo Metropolitan Institute of Medical Science |
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Principal Investigator |
TANAKA Tomoko 公益財団法人東京都医学総合研究所, 精神行動医学研究分野, 研究員 (40578986)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | アルツハイマー病 / 血管障害 / ミクログリア / 血液脳関門の破綻 / 空間認知記憶の障害 / Aβプラークの形成 / 脳神経疾患 / 脳・神経 / 神経科学 / 生理学 |
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| Outline of Final Research Achievements |
Alzheimer’s disease (AD) is a major problem. Early-life factors associated with an increased risk for the clinical diagnosis of AD have recently been identified. In the present study, we investigated the involvement of early-life stress in the pathogenesis of AD using heterozygous amyloid precursor protein (APP) mutant mice (AppNL-G-F/wt) and wild-type (Appwt/wt) mice. We found that maternal-separated (MS) Appwt/wt mice showed a vessel impairment in the prefrontal cortex, while MS AppNL-G-F/wt mice additionally showed AD-like phenomenon, and severe vessel impairment. At an early stage, morphological changes were observed in the microglia of the MS AppNL-G-F/wt mice, MS Appwt/wt mice and non-MS AppNL-G-F/wt mice. Microglia activation induced by maternal separation in combination with the APP mutation may impair the vascular system, leading to AD progression. These findings therefore suggest that maternal separation results in the early induction of AD-related pathology via angiopathy.
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| Academic Significance and Societal Importance of the Research Achievements |
発達期ストレスがアルツハイマー病(AD)病態を促進することを実証した我々の結果は、ストレス誘発性のAD発症モデルマウスの作製につながったと考えられる。ADは老年期においても転居や入院などのストレスにより発症や症状悪化が報告されとおり、本モデルマウスはADの病態解明、予防法開発に重要である。また，本研究で初めてADモデルマウスで血管系の変化に先行してミクログリアの変化を同定できた。したがって、ミクログリアは新たな予防のターゲットになりうること、また、その変化は新たなADのバイオマーカーになりうることが示された。
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Report
(5 results)
Research Products
(13 results)
