Satoh Jun-Ichi, Yamamoto Yoji, Asahina Naohiro, Kitano Shouta, Kino Yoshihiro
Department of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan.
Dis Markers. 2014;2014:123165. doi: 10.1155/2014/123165. Epub 2014 Dec 8.
Alzheimer's disease (AD) is the most common cause of dementia worldwide with no curative therapies currently available. Previously, global transcriptome analysis of AD brains by microarray failed to identify the set of consistently deregulated genes for biomarker development of AD. Therefore, the molecular pathogenesis of AD remains largely unknown. Whole RNA sequencing (RNA-Seq) is an innovative technology for the comprehensive transcriptome profiling on a genome-wide scale that overcomes several drawbacks of the microarray-based approach. To identify biomarker genes for AD, we analyzed a RNA-Seq dataset composed of the comprehensive transcriptome of autopsized AD brains derived from two independent cohorts. We identified the core set of 522 genes deregulated in AD brains shared between both, compared with normal control subjects. They included downregulation of neuronal differentiation 6 (NeuroD6), a basic helix-loop-helix (bHLH) transcription factor involved in neuronal development, differentiation, and survival in AD brains of both cohorts. We verified the results of RNA-Seq by analyzing three microarray datasets of AD brains different in brain regions, ethnicities, and microarray platforms. Thus, both RNA-Seq and microarray data analysis indicated consistent downregulation of NeuroD6 in AD brains. These results suggested that downregulation of NeuroD6 serves as a possible biomarker for AD brains.
阿尔茨海默病（AD）是全球范围内痴呆最常见的病因，目前尚无治愈性疗法。此前，通过微阵列对AD大脑进行的全转录组分析未能鉴定出用于AD生物标志物开发的一组始终失调的基因。因此，AD的分子发病机制在很大程度上仍然未知。全RNA测序（RNA-Seq）是一种用于在全基因组范围内进行全面转录组分析的创新技术，它克服了基于微阵列方法的几个缺点。为了鉴定AD的生物标志物基因，我们分析了一个RNA-Seq数据集，该数据集由来自两个独立队列的尸检AD大脑的全面转录组组成。与正常对照受试者相比，我们鉴定出了在两个队列的AD大脑中均失调的522个基因的核心集。其中包括神经元分化6（NeuroD6）的下调，NeuroD6是一种参与两个队列AD大脑中神经元发育、分化和存活的碱性螺旋-环-螺旋（bHLH）转录因子。我们通过分析三个在脑区、种族和微阵列平台方面不同的AD大脑微阵列数据集，验证了RNA-Seq的结果。因此，RNA-Seq和微阵列数据分析均表明AD大脑中NeuroD6持续下调。这些结果表明，NeuroD6的下调可能是AD大脑的一种生物标志物。
