The senescence-accelerated mouse prone 8 (SAMP8) mouse model is a useful model for investigating the fundamental mechanisms involved in the age-related learning and memory deficits of Alzheimer’s disease (AD), while the SAM/resistant 1 (SAMR1) mouse model shows normal features. Recent evidence has shown that long non-coding RNAs (lncRNAs) may play an important role in AD pathogenesis. However, a comprehensive and systematic understanding of the function of AD-related lncRNAs and their associated nearby coding genes in AD is still lacking. In this study, we collected the hippocampus, the main area of AD pathological processes, of SAMP8 and SAMR1 animals and performed microarray analysis to identify aberrantly expressed lncRNAs and their associated nearby coding genes, which may contribute to AD pathogenesis. We identified 3,112 differentially expressed lncRNAs and 3,191 differentially expressed mRNAs in SAMP8 mice compared to SAMR1 mice. More than 70% of the deregulated lncRNAs were intergenic and exon sense-overlapping lncRNAs. Gene Ontology (GO) and pathway analyses of the AD-related transcripts were also performed and are described in detail, which imply that metabolic process reprograming was likely related to AD. Furthermore, six lncRNAs and six mRNAs were selected for further validation of the microarray results using quantitative PCR, and the results were consistent with the findings from the microarray. Moreover, we analyzed 780 lincRNAs (also called long “intergenic” non-coding RNAs) and their associated nearby coding genes. Among these lincRNAs, AK158400 had the most genes nearby (n = 13), all of which belonged to the histone cluster 1 family, suggesting regulation of the nucleosome structure of the chromosomal fiber by affecting nearby genes during AD progression. In addition, we also identified 97 aberrant antisense lncRNAs and their associated coding genes. It is likely that these dysregulated lncRNAs and their associated nearby coding genes play a role in the development and/or progression of AD.

衰老加速小鼠倾向于8（SAMP8）小鼠模型是用于研究与老年痴呆症（AD）的年龄相关的学习和记忆缺陷有关的基本机制的有用模型，而SAM /耐药1（SAMR1）小鼠模型显示正常功能。最近的证据表明，长的非编码RNA（lncRNA）可能在AD发病机理中起重要作用。然而，仍缺乏对AD相关lncRNAs及其相关的邻近编码基因在AD中的功能的全面和系统的理解。在这项研究中，我们收集了海马，SAMP8和SAMR1动物的AD病理过程的主要区域，并进行了微阵列分析，以鉴定异常表达的lncRNA及其相关的附近编码基因，这可能有助于AD发病。我们确定了3 与SAMR1小鼠相比，SAMP8小鼠中有112个差异表达的lncRNA和3191个差异表达的mRNA。超过70％的失调lncRNA是基因间和外显子有义重叠的lncRNA。还进行了基因本体论（GO）和AD相关转录本的途径分析，并进行了详细描述，这表明代谢过程重编程可能与AD有关。此外，使用定量PCR选择了六个lncRNA和六个mRNA用于进一步验证微阵列结果，结果与微阵列的发现相符。此外，我们分析了780个lincRNA（也称为长的“基因间”非编码RNA）及其相关的附近编码基因。在这些lincRNA中，AK158400附近的基因最多（n = 13），所有基因都属于组蛋白簇1家族，提示通过在AD进展过程中影响附近的基因来调节染色体纤维的核小体结构。此外，我们还鉴定了97个反义lncRNA及其相关的编码基因。这些失调的lncRNA及其相关的附近编码基因可能在AD的发展和/或进程中起作用。