論文

査読有り
2017年1月

Serum microRNA miR-501-3p as a potential biomarker related to the progression of Alzheimer's disease

ACTA NEUROPATHOLOGICA COMMUNICATIONS
  • Norikazu Hara
  • ,
  • Masataka Kikuchi
  • ,
  • Akinori Miyashita
  • ,
  • Hiroyuki Hatsuta
  • ,
  • Yuko Saito
  • ,
  • Kensaku Kasuga
  • ,
  • Shigeo Murayama
  • ,
  • Takeshi Ikeuchi
  • ,
  • Ryozo Kuwano

5
1
開始ページ
10
終了ページ
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1186/s40478-017-0414-z
出版者・発行元
BIOMED CENTRAL LTD

MicroRNAs (miRNAs) are attractive molecules to utilize as one of the blood-based biomarkers for neurodegenerative disorders such as Alzheimer's disease (AD) because miRNAs are relatively stable in biofluid, including serum or plasma. To determine blood miRNA biomarkers for AD with next-generation sequencing genome-wide, we first surveyed 45 serum samples. These came from 27 AD patients and 18 controls (discovery set) that underwent autopsy within two weeks after their serum sampling and were neuropathologically diagnosed. We found that three miRNAs, hsa-miR-501-3p, hsa-let-7f-5p, and hsa-miR-26b-5p, were significantly deregulated between the AD samples and the controls. The deregulation for hsa-miR-501-3p was further confirmed by quantitative reverse transcription polymerase chain reaction (PCR) in a validation set composed of 36 clinically diagnosed AD patients and 22 age-matched cognitively normal controls with a sensitivity and specificity of 53% and 100%, respectively (area under the curve = 0.82). Serum hsa-miR-501-3p levels were downregulated in AD patients, and its lower levels significantly correlated with lower Mini-Mental State Examination scores. Contrary to its serum levels, we found that hsa-miR-501-3p was remarkably upregulated in the same donors' AD brains obtained at autopsy from the discovery set. The hsa-miR-501-3p overexpression in cultured cells, which mimicked the hsa-miR-501-3p upregulation in the AD brains, induced significant downregulation of 128 genes that overrepresented the Gene Ontology terms, DNA replication, and the mitotic cell cycle. Our results suggest that hsa-miR-501-3p is a novel serum biomarker that presumably corresponds to pathological events occurring in AD brains.

リンク情報
DOI
https://doi.org/10.1186/s40478-017-0414-z
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28137310
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000392964200001&DestApp=WOS_CPL
ID情報
  • DOI : 10.1186/s40478-017-0414-z
  • ISSN : 2051-5960
  • PubMed ID : 28137310
  • Web of Science ID : WOS:000392964200001

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