| Project/Area Number |
26870209
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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 |
Nerve anatomy/Neuropathology
Neurology
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| Research Institution | Niigata University |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | アルツハイマー病 / 神経活動 / アミロイド前駆体蛋白 / Aβ / タウ蛋白 / アミロイドβ / タウ蛋白リン酸化 / Alzheimer's disease / Neuronal activity / Amyloid beta / Phosphorylated tau |
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| Outline of Final Research Achievements |
Alzheimer’s disease (AD) is the most common cause of dementia, which is pathologically characterized by extracellular deposits of β-amyloid (Aβ) and intracellular accumulation of hyperphosphorylated tau. Hippocampal neurons showing hyperactivity early in the disease course send those axons to the default-mode network where Aβ accumulates remarkably in the brain. Aβ is derived from amyloid precursor protein (APP) by sequential cleavages.
Here we performed in vitro assay with murine neuroblastoma cells and rat cortical neuron primary cultures. After glutamatergic stimulation, we found that full length APP was reduced in a neuronal activity dependent manner. In addition, C-terminal fragments of APP increased after the stimulation, suggesting that the stimulation enhanced β-cleavage. We previously showed Aβ-dependent tau phosphorylation by using the coculture system. Taken together, neuronal activity may affect APP processing and tau phosphorylation in neuronal network.
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