| Project/Area Number |
23390187
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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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 | Osaka University |
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Principal Investigator |
SATO Naoyuki 大阪大学, 医学(系)研究科(研究院), 准教授 (70372612)
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| Co-Investigator(Kenkyū-buntansha) |
UCHIO Kozue 医薬基盤研究所, 難病・疾患資源研究部, 主任研究員 (70373397)
UEDA Hironori 大阪大学, 医学研究科, 特任准教授 (90543463)
MURAYAMA Shigeo 東京都健康長寿医療センター, 研究部長 (50183653)
林 真一郎 独立行政法人国立循環器病研究センター, その他部局等, 研究員 (20396740)
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| Co-Investigator(Renkei-kenkyūsha) |
HAYASHI Shinichiro 国立循環器病センター, 病院, 医師 (20396740)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000)
Fiscal Year 2013: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2012: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2011: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
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| Keywords | 糖尿病 / アルツハイマー病 / 神経科学 / 分子生物学 / 病理学 / 認知症 / 脳科学 / ベータ・アミロイド / タウ・リン酸化 / 恒常性破綻 / βアミロイド / インスリン・シグナル / タウ / 老人斑 / 神経原線維変化 |
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| Research Abstract |
Epidemiological studies suggest that diabetes mellitus increases the risk of onset of Alzheimer disease (AD). However, the underlying mechanisms have not been fully understood. Six months on a high fat diet increased Abeta40 in B6C mice brain. To investigate the effects of diabetes on AD, we further analyzed the phenotypes of APP+ob/ob mice, which showed the increased cerebral amyloid angiopathy and impaired insulin signaling, especially focusing on tau phosphorylation. 18 month old APP+ob/ob mice showed highly increased level of tau phosphorylation in the brain. Tau phosphorylation is increased by diabetes in APP mice, suggesting that Abeta is prerequisite, but insufficient to cause tau phosphorylation in vivo. Abeta accumulation, insulin signaling and tau phosphorylation might play essential roles in the pathological interaction between AD and diabetes.These results suggest that diabetes disrupts homeostasis against AD.
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