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评估阿尔茨海默病和额颞叶变性中的环状 RNA。

Assessing circular RNAs in Alzheimer's disease and frontotemporal lobar degeneration.

机构信息

Genetics of Neurodegenerative Disorders Unit, Sant Pau Biomedical Research Institute, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; CIBERNED, Center for Networked Biomedical Research into Neurodegenerative Diseases, Madrid, Spain.

Neurological Tissue Bank of the Biobanc-Hospital Clinic-IDIBAPS, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.

出版信息

Neurobiol Aging. 2020 Aug;92:7-11. doi: 10.1016/j.neurobiolaging.2020.03.017. Epub 2020 Apr 1.

Abstract

A circular-transcriptome-wide study has recently linked differential expression of circular RNAs (circRNAs) in brain tissue with Alzheimer's disease (AD). We aimed at replicating the major findings in an independent series of sporadic and familial AD. We also included cases with frontotemporal lobar degeneration (FTLD), comprising brain specimens with TDP-43 aggregates (FTLD-TDP43) and samples that presented Tau accumulation (FTLD-Tau). Using a quantitative polymerase chain reaction approach, we evaluated 8 circRNAs that surpassed the significant threshold in the former meta-analysis (circHOMER1, circDOCK1, circFMN1, circKCNN2, circRTN4, circMAN2A1, circMAP7, and circPICALM). Average expression changes between patients with AD and controls followed the same directions as previously reported. We also confirmed an exacerbated alteration in circRNA expression in the familial AD group compared with the sporadic forms. Two circRNAs (circHOMER1 and circKCNN2) also showed significant expression alterations in the group of FTLD-Tau and FTLD-TDP43, respectively. Overall, these results reinforce the conception that expression of circRNAs is different in AD, and also suggest a wider involvement of this particular class of RNA in other neurodegenerative dementias.

摘要

一项环状转录组全谱研究最近将环状 RNA(circRNAs)在脑组织中的差异表达与阿尔茨海默病(AD)联系起来。我们旨在在一个独立的散发性和家族性 AD 系列中复制主要发现。我们还包括额颞叶变性(FTLD)的病例,包括具有 TDP-43 聚集物的脑标本(FTLD-TDP43)和表现出 Tau 积累的样本(FTLD-Tau)。我们使用定量聚合酶链反应方法评估了在前一项荟萃分析中超过显著阈值的 8 个 circRNAs(circHOMER1、circDOCK1、circFMN1、circKCNN2、circRTN4、circMAN2A1、circMAP7 和 circPICALM)。AD 患者和对照组之间的平均表达变化与之前报道的方向相同。我们还证实了与散发性 AD 相比,家族性 AD 组中 circRNA 表达的改变更为明显。两个 circRNAs(circHOMER1 和 circKCNN2)在 FTLD-Tau 和 FTLD-TDP43 组中也表现出显著的表达改变。总的来说,这些结果强化了 AD 中 circRNAs 表达不同的概念,并表明这种特殊类 RNA 更广泛地参与了其他神经退行性痴呆。

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