| Budget Amount *help |
¥25,220,000 (Direct Cost: ¥19,400,000、Indirect Cost: ¥5,820,000)
Fiscal Year 2013: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2012: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2011: ¥10,920,000 (Direct Cost: ¥8,400,000、Indirect Cost: ¥2,520,000)
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| Research Abstract |
Experimental studies of Alzheimer's disease (AD) have largely depended on transgenic (Tg) mice overexpressing amyloid precursor protein (APP). These mice, however, suffer from artificial phenotypes because not only amyloid beta peptide (Abeta) but also other APP fragments are overproduced. To overcome these drawbacks, we generated knockin mice that harbor Swedish and Iberian mutations in the APP gene, and demonstrated that these animals start accumulating Abetaat 6 months and show memory impairment at 18 months without APP overexpression.
We also generated mice containing an additional Arctic mutation; these started depositing Abeta at 2 months and showed memory impairment at 6 months with aggressive neuroinflammation. We provide the research community with these lines in order to distinguish facts from artifacts in APP-Tg mice and to identify pathological mechanisms upstream and downstream of Abeta deposition.
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