| Project/Area Number |
18590930
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Niigata University |
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Principal Investigator |
IKEUCHI Takeshi Niigata University, Brain Research Institute, 助教 (20372469)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥630,000)
Fiscal Year 2007: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | Alzheimer disease / cholesterol / statin / amyloid precursor protein / tau / 認知症 / 脳神経疾患 / 神経科学 / 脂質 / 薬理学 |
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| Research Abstract |
Disease-modifying therapy has not been established in Alzheimer disease, in which ardinal pathological features include the accumulation of β-amyloid(Aβ) and phosphorylated tau forming senile plaque and neurofibrillary tangles, respectively. Previous epidemiological studies have suggested there is close link between impaired cholesterol metabolism and development of Alzheimer disease. Furthermore, amyloidogenesis occurs in cholesterol-rich membrane domains. Statins that inhibit cholesterol biosynthesis and have potential other multiple actions called pleiotropic effects, are the most widely used cholesterol-lowering agents. They
In this study, I investigated the effects of stain on modulation of β-amyloid and phosphorylated tau production using culture cells. SHSY-5Y and Neuro2a cells that stably express either amyloid precursor protein (APP) or tau were initially established for further assay. When cells were incubated with statin, the levels of full-length APP and APP C-terminal fragments were elevated. At high concentration of statin, Aβ42/40 ratio was markedly increased. Total and phosphorylated tau levels were apparently unaffected by statin treatment. These results suggest that cell-permeable statin have an effect on APP metabolism.
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