阿尔兹海默症（AD）是常见一种神经退行性变，可能用老年痴呆来描述这种疾病更容易被理解，AD是常见的一种老年痴呆的类型，很多名人如拳王阿里，美国总统里根等。不仅严重影响患者的生活质量，而且增加患者家属的经济负担。但其发病机制及治疗方法到目前为止尚不清楚。

对其分子机制的研究有助对其发病机制的更深入了解，也有助于发现新的治疗策略。

摘要翻译

鉴定LncRNA-miRNA-mRNA网络研究阿尔茨海默病的发病机制和治疗策略

鉴定LncRNA-miRNA-mRNA网络研究阿尔茨海默病的发病机制和治疗策略。阿尔茨海默病(AD)是导致痴呆症的最常见原因，它会导致老年脑的神经元损伤和认知功能恶化。有证据表明非编码RNA参与了AD相关的病理生理学机制。

AD和LncRNA相关的竞争内源RNA(CERNA)网络之间的潜在联系已经被揭示。然而，至今仍没有全基因组研究确定与AD相关的LncRNA-CERNA对。

为此，我们采用深层RNA测序的方法，系统地研究了AD模型小鼠(APP/PS1)脑内与LncRNA相关的CERNA网络。

我们的结果分别鉴定了48789和3025个显著失调的LncRNA、miRNAs和mRNAs，并在APP/PS1脑中构建了迄今为止最全面的与LncRNA相关的CERNA网络。GO分析显示，已识别的网络从不同的来源，如突触和树突，参与调控AD的发展。经过严格筛选，该AD小鼠模型中与lncRNA相关的CERNA网络被发现主要参与突触可塑性和记忆(AKAP5)和调节淀粉样蛋白(Aβ)诱导的神经炎症(KLF4)。

这项研究首次系统地剖析了APP/PS1小鼠大脑中与LncRNA相关的CERNA图谱。鉴别出的与LncRNA相关的CERNA网络有助于AD诊断和提出未来治疗的新策略。关键词：APP/PS1小鼠；阿尔茨海默病；RNA测序；CERNA网络；LncRNA。

原文摘要

Identifying lncRNA-miRNA-mRNA Networks to Investigate Alzheimer's Disease Pathogenesis and Therapy Strategy

Alzheimer's disease (AD), the most common cause of dementia, leads to neuronal damage and deterioration of cognitive functions in aging brains. There is evidence suggesting the participation of noncoding RNAs in AD-associated pathophysiology. A potential linkage between AD and lncRNA-associated competing endogenous RNA (ceRNA) networks has been revealed. Nevertheless, there are still no genome-wide studies which have identified the lncRNA-associated ceRNA pairs involved in AD. For this reason, deep RNA-sequencing was performed to systematically investigate lncRNA-associated ceRNA mechanisms in AD model mice (APP/PS1) brains. Our results identified 487, 89, and 3,025 significantly dysregulated lncRNAs, miRNAs, and mRNAs, respectively, and the most comprehensive lncRNA-associated ceRNA networks to date are constructed in the APP/PS1 brain. GO analysis revealed the involvement of the identified networks in regulating AD development from distinct origins, such as synapses and dendrites. Following rigorous selection, the lncRNA-associated ceRNA networks in this AD mouse model were found to be mainly involved in synaptic plasticity as well as memory (Akap5) and regulation of amyloid-β (Aβ)-induced neuroinflammation (Klf4). This study presents the first systematic dissection of lncRNA-associated ceRNA profiles in the APP/PS1 mouse brain. The identified lncRNA-associated ceRNA networks could provide insights that facilitate AD diagnosis and future treatment strategies.

Keywords: APP/PS1 mouse; Alzheimer’s disease (AD); RNA-sequencing; ceRNA n