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

Pichler, Sabrina, Gu, Wei, Hartl, Daniela, Gasparoni, Gilles, Leidinger, Petra, Keller, Andreas, Meese, Eckart, Mayhaus, Manuel, Hampel, Harald, Riemenschneider, Matthias·2017·Neurobiology of Aging

Abstract

MicroRNAs (miRNAs) are small noncoding 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 semiquantitative real-time polymerase chain reaction (PCR) in independent prefrontal cortex. Furthermore, we separated gray 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 gray matter AD samples. We further identified 10 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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Crossref · 10.1016/j.neurobiolaging.2016.09.019

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Metadata

Authors
Pichler, S., Gu, W., Hartl, D., Gasparoni, G., Leidinger, P., Keller, A., Meese, E., Mayhaus, M., Hampel, H., & Riemenschneider, M.
Venue
Neurobiology of Aging
Publisher
Elsevier BV
Published
2017-02
Volume
50
Pages
167.e1-167.e10
ISSN
0197-4580
Cited by
108
References
5
Language
en
Funders
  • German Federal Ministry of Education and Research
  • National Genome Research Network (01GS08125)
  • Helmholtz Alliance for Mental Health in an Aging Society (Ha-15)

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