Distinct Hippocampal Expression Profiles of Long Non-coding RNAs in an Alzheimer\u2019s Disease Model

Bo Yang,Yang Wang,Yucheng Cao,Xingui Xiong,Zhe Wang,Zi-An Xia,Wei Gong,Bingwu Zhong,Chenxia Sheng,Weijun Peng

doi:10.1007/s12035-016-0038-5

Abstract

Alzheimer’s disease (AD), the most prevalent form of dementia worldwide, is a complex neurodegenerative disease characterized by the progressive loss of memory and other cognitive functions. The pathogenesis of AD is not yet completely understood. Although long non-coding RNAs (lncRNAs) have recently been shown to play a role in AD pathogenesis, the specific influences of lncRNAs in AD remain largely unknown; in particular, hippocampal lncRNA expression profiles in AD rats are lacking. In this study, microarray analysis was performed to investigate the hippocampal expression patterns of dysregulated lncRNAs in a rat model of AD. A total of 315 lncRNAs and 311 mRNAs were found to be significantly dysregulated in the AD model (≥2.0 fold, p < 0.05). Then, quantitative real-time PCR was used to validate the expression of selected lncRNAs and mRNAs. Bioinformatics tools and databases were employed to explore the potential lncRNA functions. This is the first study to comprehensively identify dysregulated hippocampal lncRNAs in AD and to demonstrate the involvement of different lncRNA expression patterns in the hippocampal pathogenesis of AD. This information will enable further research on the pathogenesis of AD and facilitate the development of novel AD therapeutics targeting lncRNAs.

Highlights

Alzheimer’s disease (AD) is considered to be the most common cause of dementia; AD is a progressive neurodegenerative disease characterized by the accumulation of amyloid-β(Aβ) plaques and neurofibrillary tangles, synaptic and neuronal loss, and cognitive decline [1]
Zhou et al identified AD-associated Long non-coding RNAs (lncRNAs) based on post-mortem tissue samples of AD patients [14]
M. magistri et al identified several annotated and non-annotated lincRNAs that are differentially expressed in the hippocampus in late-onset

Summary

Introduction

Alzheimer’s disease (AD) is considered to be the most common cause of dementia; AD is a progressive neurodegenerative disease characterized by the accumulation of amyloid-β(Aβ) plaques and neurofibrillary tangles, synaptic and neuronal loss, and cognitive decline [1]. No currently available therapeutic strategies for AD slow or stop the neuronal damage that causes AD symptoms and eventually results in death [3, 4]. There is an urgent need for novel strategies of improving our mechanistic understanding of AD, which could lead to the discovery of novel therapeutic targets. Multiple lines of evidence have linked lncRNA mutations and dysregulation with diverse human diseases, ranging from different types of cancer and neurodegeneration to gynaecological diseases [7,8,9]

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Conclusion