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Neuronal activity promotes tau phosphorylation via enhancement of APP processing

Research Project

Project/Area Number 26870209
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Nerve anatomy/Neuropathology
Neurology
Research InstitutionNiigata University

Principal Investigator

Kasuga Kensaku  新潟大学, 研究推進機構, 助教 (70547546)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
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)
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
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.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (6 results)

All 2015 2014 Other

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (4 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Remarks (1 results)

  • [Journal Article] Systematic review and meta-analysis of Japanese familial Alzheimer's disease and FTDP-17.2015

    • Author(s)
      Kasuga,et al
    • Journal Title

      Journal of Human Genetics

      Volume: in press Issue: 5 Pages: 1-3

    • DOI

      10.1038/jhg.2015.15

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Neuronal activity enhances APP processing in cultured neurons2015

    • Author(s)
      Saito K, Kasuga K and Ikeuchi T
    • Organizer
      Neuroscience annual meeting 2015
    • Place of Presentation
      McCormick Place, IL, USA
    • Year and Date
      2015-10-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Systematic review of Japanese familial Alzheimer’s disease and FTDP-172015

    • Author(s)
      Kasuga K, Kikuchi M, Tokutake T, Nakaya A, Tezuka T, Tsukie T, Hara N, Miyashita A, Kuwano R and Ikeuchi T
    • Organizer
      Alzheimer’s Association International Conference 2015
    • Place of Presentation
      Convention Center, Washington DC, USA
    • Year and Date
      2015-07-18
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 本邦における家族アルツハイマー病データベース(Japanese Familial Alzheimer's Disease database, JFADdb)の構築2015

    • Author(s)
      春日健作、菊地正隆、徳武孝允、手塚敏之、月江珠緒、原範和、宮下哲典、中谷明弘、桑野良三、池内健
    • Organizer
      第56回日本神経学会学術大会
    • Place of Presentation
      朱鷺メッセ、新潟
    • Year and Date
      2015-05-20
    • Related Report
      2015 Annual Research Report
  • [Presentation] ニワトリと卵, 神経活動とAβ放出2014

    • Author(s)
      春日健作
    • Organizer
      第33回日本認知症学会学術集会
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Year and Date
      2014-10-29 – 2014-11-01
    • Related Report
      2014 Research-status Report
    • Invited
  • [Remarks] http://alzdb.bri.niigata-u.ac.jp/

    • Related Report
      2015 Annual Research Report

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Published: 2014-04-04   Modified: 2017-05-10  

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