論文

査読有り 国際誌
2019年12月

Network-guided analysis of hippocampal proteome identifies novel proteins that colocalize with Aβ in a mice model of early-stage Alzheimer's disease.

Neurobiology of disease
  • Aderemi Caleb Aladeokin
  • ,
  • Tomoko Akiyama
  • ,
  • Ayuko Kimura
  • ,
  • Yayoi Kimura
  • ,
  • Aoi Takahashi-Jitsuki
  • ,
  • Haruko Nakamura
  • ,
  • Hiroko Makihara
  • ,
  • Daiki Masukawa
  • ,
  • Jun Nakabayashi
  • ,
  • Hisashi Hirano
  • ,
  • Fumio Nakamura
  • ,
  • Takashi Saito
  • ,
  • Takaomi Saido
  • ,
  • Yoshio Goshima

132
開始ページ
104603
終了ページ
104603
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.nbd.2019.104603

Alzheimer's disease (AD) is an incurable neurodegenerative disease characterized by memory loss and neurotoxic amyloid beta (Aβ) plaques accumulation. Numerous pharmacological interventions targeting Aβ plaques accumulation have failed to alleviate AD. Also, the pathological alterations in AD start years before the onset of clinical symptoms. To identify proteins at play during the early stage of AD, we conducted proteomic analysis of the hippocampus of young AppNL-F mice model of AD at the preclinical phase of the disease. This was followed by interactome ranking of the proteome into hubs that were further validated in vivo using immunoblot analysis. We also performed double-immunolabeling of these hub proteins and Aβ to quantify colocalization. Behavioral analysis revealed no significant difference in memory performance between 8-month-old AppNL-F and control mice. The upregulation and downregulation of several proteins were observed in the AppNL-F mice compared to control. These proteins corresponded to pathways and processes related to Aβ clearance, inflammatory-immune response, transport, mitochondrial metabolism, and glial cell proliferation. Interactome analysis revealed several proteins including DLGP5, DDX49, CCDC85A, ADCY6, HEPACAM, HCN3, PPT1 and TNPO1 as essential proteins in the AppNL-F interactome. Validation by immunoblot confirmed the over-expression of these proteins except HCN3 in the early-stage AD mice hippocampus. Immunolabeling revealed a significant increase in ADCY6/Aβ and HEPACAM/Aβ colocalized puncta in AppNL-F mice compared to WT. These data suggest that these proteins may be involved in the early stage of AD. Our work suggests new targets and biomarkers for AD diagnosis and therapeutic intervention.

リンク情報
DOI
https://doi.org/10.1016/j.nbd.2019.104603
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31494281
ID情報
  • DOI : 10.1016/j.nbd.2019.104603
  • PubMed ID : 31494281

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