| Project/Area Number |
24700383
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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 |
Neurochemistry/Neuropharmacology
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| Research Institution | Iwate Medical University |
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Principal Investigator |
ZOU KUN 岩手医科大学, 薬学部, 講師 (40450837)
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| Co-Investigator(Renkei-kenkyūsha) |
KOMANO Hiroto 岩手医科大学, 薬学部, 教授 (40170378)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | アルツハイマー病 / アミロイドベータ蛋白 / アンギオテンシン変換酵素 / アミロイド沈着 / Aβ43変換活性 |
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| Research Abstract |
The longer and neurotoxic species of amyloid beta-protein (Abeta), Abeta42 and Abeta43, contribute to Abeta accumulation in Alzheimer's disease (AD) pathogenesis and are considered to be the primary cause of the disease. In contrast, Abeta40, inhibits amyloid deposition and may have neuroprotective effects. Herein, we provide evidence that Abeta43 deposition appears earlier than Abeta42 and Abeta40 deposition in the brain of mutant amyloid precursor protein transgenic (APPtg) mice, suggesting that Abeta43 is the earliest depositing Abeta species. In addition, we found increased Abeta43 levels and Abeta43/Abeta42 ratio in the serum of AD patients, which may be used as diagnostic blood biomarkers for AD. We further identified the brain Abeta43-to-Abeta42-converting enzyme as ACE2. Notably, the combination of ACE2 and ACE could convert Abeta43 to Abeta40. Thus, maintaining brain ACE2 and ACE activities may be important for preventing brain amyloid neurotoxicity and deposition in AD.
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