The miRNome of Alzheimer’s disease: consistent downregulation of the miR-132/212 cluster

Publication date: Available online 3 October 2016
Source:Neurobiology of Aging
Author(s): Sabrina Pichler, Wei Gu, Daniela Hartl, Gilles Gasparoni, Petra Leidinger, Andreas Keller, Eckart Meese, Manuel Mayhaus, Harald Hampel, Matthias Riemenschneider
MicroRNAs (miRNAs) are small non-coding RNA molecules, with essential functions in RNA silencing and post-transcriptional regulation of gene expression. MiRNAs appear to regulate the development and function of the nervous system. Alterations of miRNA expression have been associated with Alzheimer's disease (AD). To characterize the AD miRNA signature we examined genome wide miRNA and mRNA expression patterns in the temporal cortex of AD and control samples. We validated our miRNA results by semi-quantitative real-time PCR in independent prefrontal cortex. Further, we separated grey and white matter brain sections to identify the cellular origin of the altered miRNA expression. We observed genome wide downregulation of hsa-miR-132-3p and hsa-miR-212-3p in AD with a stronger decrease in grey matter AD samples. We further identified ten differently expressed transcripts achieving genome wide levels of significance. Significantly deregulated miRNAs and mRNAs were correlated and examined for potential binding sites (in silico). This miRNome-wide study in AD provides supportive evidence and corroborates an important contribution of miR-132/212 and corresponding target mRNAs to the pathogenesis of AD.



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