ナカムラ　フミオ   Nakamura Fumio   中村　史雄    所属   医学部 医学科    職種   教授・基幹分野長
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Network-guided analysis of hippocampal proteome identifies novel proteins that colocalize with Aβ in a mice model of early-stage Alzheimer's disease.
掲載誌名	正式名：Neurobiology of disease 略　 称：Neurobiol Dis ISSNコード：1095953X/09699961
掲載区分	国外
巻・号・頁	132,pp.104603
著者・共著者	Aladeokin Aderemi Caleb, Akiyama Tomoko, Kimura Ayuko, Kimura Yayoi, Takahashi-Jitsuki Aoi, Nakamura Haruko, Makihara Hiroko, Masukawa Daiki, Nakabayashi Jun, Hirano Hisashi, Nakamura Fumio, Saito Takashi, Saido Takaomi, Goshima Yoshio
発行年月	2019/12
概要	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.
DOI	10.1016/j.nbd.2019.104603
PMID	31494281