Identification of miRNA changes in Alzheimer's disease brain and CSF yields putative biomarkers and insights into disease pathways

被引:785
作者
Cogswell, John P. [1 ]
Ward, James
Taylor, Ian A. [2 ]
Waters, Michelle [3 ]
Shi, Yunling
Cannon, Brian [4 ]
Kelnar, Kevin [4 ]
Kemppainen, Jon [4 ]
Brown, David [4 ]
Chen, Caifu [5 ]
Prinjha, Rab K. [6 ]
Richardson, Jill C. [6 ]
Saunders, Ann M. [1 ]
Roses, Allen D. [1 ]
Richards, Cynthia A. [7 ]
机构
[1] GlaxoSmithKline Inc, Dept Pharmacogenet, Res Triangle Pk, NC 27709 USA
[2] GlaxoSmithKline Inc, Dept Mol Discovery Res Informat, Core Technol Grp, Res Triangle Pk, NC 27709 USA
[3] GlaxoSmithKline Inc, Dept Mol Discovery Res Informat, Metab Discovery Technol Grp, Res Triangle Pk, NC 27709 USA
[4] Asuragen Inc, Austin, TX USA
[5] Appl Biosyst Inc, Mol Cell Biol RandD, Foster City, CA 94404 USA
[6] GlaxoSmithKline Inc, Neurol CEDD, Harlow, Essex, England
[7] GlaxoSmithKline Inc, Dept Mol Discovery Res, Infect Dis Discovery Technol Grp, Res Triangle Pk, NC 27709 USA
关键词
Alzheimer's disease; inflammation; insulin signaling; microRNA; neurogenesis;
D O I
10.3233/jad-2008-14103
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
MicroRNAs have essential functional roles in brain development and neuronal specification but their roles in neurodegenerative diseases such as Alzheimer's disease ( AD) is unknown. Using a sensitive qRT-PCR platform we identified regional and stage-specific deregulation of miRNA expression in AD patient brains. We used experimental validation in addition to literature to reveal how the deregulated brain microRNAs are biomarkers for known and novel pathways in AD pathogenesis related to amyloid processing, neurogenesis, insulin resistance, and innate immunity. We additionally recovered miRNAs from cerebrospinal fluid and discovered AD-specific miRNA changes consistent with their role as potential biomarkers of disease.
引用
收藏
页码:27 / 41
页数:15
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