論文

査読有り 本文へのリンクあり 国際誌
2021年3月9日

Extracellular Release of ILEI/FAM3C and Amyloid-β Is Associated with the Activation of Distinct Synapse Subpopulations

Journal of Alzheimer's Disease
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回数 : 54
  • Masaki Nakano
  • Yachiyo Mitsuishi
  • Lei Liu
  • Naoki Watanabe
  • Emi Hibino
  • Saori Hata
  • Takashi Saito
  • Takaomi C. Saido
  • Shigeo Murayama
  • Kensaku Kasuga
  • Takeshi Ikeuchi
  • Toshiharu Suzuki
  • Masaki Nishimura
  • 全て表示

80
1
開始ページ
159
終了ページ
174
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.3233/jad-201174
出版者・発行元
IOS Press

Background: Brain amyloid-β (Aβ) peptide is released into the interstitial fluid (ISF) in a neuronal activity-dependent manner, and Aβ deposition in Alzheimer’s disease (AD) is linked to baseline neuronal activity. Although the intrinsic mechanism for Aβ generation remains to be elucidated, interleukin-like epithelial-mesenchymal transition inducer (ILEI) is a candidate for an endogenous Aβ suppressor. Objective: This study aimed to access the mechanism underlying ILEI secretion and its effect on Aβ production in the brain. Methods: ILEI and Aβ levels in the cerebral cortex were monitored using a newly developed ILEI-specific ELISA and in vivo microdialysis in mutant human Aβ precursor protein-knockin mice. ILEI levels in autopsied brains and cerebrospinal fluid (CSF) were measured using ELISA. Results: Extracellular release of ILEI and Aβ was dependent on neuronal activation and specifically on tetanus toxin-sensitive exocytosis of synaptic vesicles. However, simultaneous monitoring of extracellular ILEI and Aβ revealed that a spontaneous fluctuation of ILEI levels appeared to inversely mirror that of Aβ levels. Selective activation and inhibition of synaptic receptors differentially altered these levels. The evoked activation of AMPA-type receptors resulted in opposing changes to ILEI and Aβ levels. Brain ILEI levels were selectively decreased in AD. CSF ILEI concentration correlated with that of Aβ and were reduced in AD and mild cognitive impairment. Conclusion: ILEI and Aβ are released from distinct subpopulations of synaptic terminals in an activity-dependent manner, and ILEI negatively regulates Aβ production in specific synapse types. CSF ILEI might represent a surrogate marker for the accumulation of brain Aβ.

リンク情報
DOI
https://doi.org/10.3233/jad-201174
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/33492290
URL
https://content.iospress.com/download?id=10.3233/JAD-201174
ID情報
  • DOI : 10.3233/jad-201174
  • ISSN : 1387-2877
  • eISSN : 1875-8908
  • PubMed ID : 33492290

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