Background

MicroRNAs (miRNAs) emerged as regulatory elements, with up to 70 % of all miRNAs found in the brain, playing key roles in the onset of Alzheimer’s disease (AD).

Objective

to broadly assess the expression levels of miRNAs in post-mortem brain (PMB) samples of individuals deceased with or without AD.

Methods

A high-throughput microarray platform was used to sketch miRNA samples isolated from superior and middle temporal gyrus of A+T+ AD cases, compared to samples from age- and sex-matched AD-devoid donors, all pulled from the University of São Paulo’s Brain Biobank. The miRNAs identified by microarray were subjected to validation with specific qRT-PCR assays employing independent PMB samples.

Results

The analyses yielded 6 miRNAs differentially expressed (miR-30e_3p; miR-365b_5p; miR-664_3p; miR-1202; miR-4286; miR-4449), and their interplay with specific AD-related genes and signaling pathways was explored using bioinformatics analyses (including the KEGG package, mirPath v.3). In the end, 3 miRNAs, 7 target genes and 11 pathways were found closely interrelated and implicated with the AD pathophysiology.

Conclusion

A dysregulation on a subset of these miRNAs appear to affect a range of genes (notably PTEN) and pathways (emphasis to PI3K-AKT) so to provide grounds for neuronal death by apoptotic signaling, autophagy and/or oxidative damage.

中文翻译：

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全基因组分析和死后脑 microRNA 在阿尔茨海默病中的预测意义。

背景

MicroRNA (miRNA) 作为调控元件出现，在大脑中发现的所有 miRNA 中高达 70%，在阿尔茨海默病 (AD) 的发病中起着关键作用。

客观的

广泛评估患有或不患有 AD 的个体死后脑 (PMB) 样本中miRNA 的表达水平。

方法

高通量微阵列平台用于绘制从 A+T+ AD 病例的颞上回和中颞回分离的 miRNA 样本，并与年龄和性别匹配的无 AD 供体的样本进行比较，所有样本均来自圣保罗大学的大脑生物银行。通过使用独立 PMB 样本的特定 qRT-PCR 检测对微阵列鉴定的 miRNA 进行验证。

结果

分析产生了 6 个差异表达的 miRNA（miR-30e_3p；miR-365b_5p；miR-664_3p；miR-1202；miR-4286；miR-4449），并使用生物信息学分析探索了它们与特定 AD 相关基因和信号通路的相互作用（包括 KEGG 包，mirPath v.3）。最终发现3个miRNA、7个靶基因和11条通路与AD病理生理密切相关。

结论

这些 miRNA 子集的失调似乎会影响一系列基因（特别是 PTEN）和通路（重点是 PI3K-AKT），从而为通过凋亡信号传导、自噬和/或氧化损伤导致神经元死亡提供依据。