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The miRNome of Alzheimer's disease: consistent downregulation of the miR-132/212 cluster
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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miR-212-5p was found decreased in several other neurodegenerative diseases such as AD, Huntington's disease, and PD.
“Moreover, miR-212-5p was found decreased in several other neurodegenerative diseases such as AD, Huntington’s disease, and PD [62, 66, 69–75], indicating a key role in neurodegenerative diseases.”
From A role for astrocytic miR-129-5p in frontotemporal dementia (2025) · cites this paper as [72]
Substantial recent evidence has demonstrated that microRNAs are dysregulated already early on in AD pathology.
“Substantial recent evidence has demonstrated that microRNAs (miRNAs) are dysregulated already early on in AD pathology [2–7].”
From microRNA-132 attenuates inflammation in induced pluripotent stem cell-derived microglia from Alzheimer’s disease patients (2026) · cites this paper as [7]
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A role for astrocytic miR-129-5p in frontotemporal dementia
Kaurani, L., Pradhan, R., Schröder, S., Burkhardt, S., Schuetz, A.-L., Krüger, D. M., Pena, T., Heutink, P., Sananbenesi, F., & Fischer, A. (2025) · Translational Psychiatry · doi:10.1038/s41398-025-03338-y · Cited by 10
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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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