| Project/Area Number |
16K09248
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General internal medicine(including psychosomatic medicine)
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| Research Institution | Oita University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
花岡 拓哉 大分大学, 医学部, 講師 (40433057)
麻生 泰弘 大分大学, 医学部, 助教 (80555194)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
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| Keywords | Neurovascular unit / Alzheimer’s disease / MCI / MRI / PIB-PET / FDG-PET / Blood-brain barrier / Biomarker / 大脳白質病変 / 血液脳関門障害 / MMP / TIMP / 認知症予防 / 血管危険因子 / neurovascular unit / アミロイドPET / 軽度認知障害 / 大脳白質変性 / Neurovascular Unit / アルツハイマー病 / バイオマーカー |
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| Outline of Final Research Achievements |
White matter lesions are associated with vascular risk factors, especially hypertension. These lesions affect cognitive function and brain function in patients with Alzheimer's disease at the early stage of disease. Amyloid-positive MCI subjects with cerebral white matter lesions showed increased MMP2, 8, 9, and fibrinogen as well as plasminogen and decreased TIMPs 1 and 2 in the plasma, which related to blood-brain barrier (BBB) damage. In addition, they showed increased MMP12 and decreased TIMP4 in cerebrospinal fluid. The severity of cerebral white matter lesions and BBB damage markers do not correlate with cerebral amyloid deposition. Therefore, we speculated that the BBB damage due to arteriosclerosis and chronic inflammation is related to pathogenesis of cerebral white matter lesions in Alzheimer's disease. Moreover, BBB damage and white matter lesions may affect independently the brain function and cognitive function.
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| Academic Significance and Societal Importance of the Research Achievements |
アルツハイマー型認知症の前段階であるMCI due to ADでは、生活習慣病によってNeurovascular unit (NVU)の破綻が生じ、虚血性大脳白質変性が生じていることが推測された。さらに、この大脳白質病変は、前頭葉機能および認知機能障害の進行に影響することが明らかとなった。この研究成果により、NVUの関連分子が症状進行のバイオマーカーだけでなく、新規治療薬のターゲットとなる可能性が示された。従って、本研究はNVU protectionによる脳保護療法という新たな予防法の開発に繋がる。
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