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. 2007 Dec 20:1:263-74.
doi: 10.4137/grsb.s361.

MicroRNA expression in Alzheimer blood mononuclear cells

Hyman M Schipper  1 , Olivier C Maes, Howard M Chertkow, Eugenia Wang
Affiliations

MicroRNA expression in Alzheimer blood mononuclear cells

Hyman M Schipper et al. Gene Regul Syst Bio. .

Abstract

Various coding genes representing multiple functional categories are downregulated in blood mononuclear cells (BMC) of patients with sporadic Alzheimer disease (AD). Noncoding microRNAs (miRNA) regulate gene expression by degrading messages or inhibiting translation. Using BMC as a paradigm for the study of systemic alterations in AD, we investigated whether peripheral miRNA expression is altered in this condition. MicroRNA levels were assessed using the microRNA microarray (MMChip) containing 462 human miRNA, and the results validated by real time PCR. Sixteen AD patients and sixteen normal elderly controls (NEC) were matched for ethnicity, age, gender and education. The expression of several BMC miRNAs was found to increase in AD relative to NEC levels, and may differ between AD subjects bearing one or two APOE4 alleles. As compared to NEC, miRNAs significantly upregulated in AD subjects and confirmed by qPCR were miR-34a and 181b. Predicted target genes downregulated in Alzheimer BMC that correlated with the upregulated miRNAs were largely represented in the functional categories of Transcription/Translation and Synaptic Activity. Several miRNAs targeting the same genes were within the functional category of Injury response/Redox homeostasis. Taken together, induction of microRNA expression in BMC may contribute to the aberrant systemic decline in mRNA levels in sporadic AD.

Keywords: Alzheimer disease; gene expression; microarray; neurodegeneration; noncoding small RNA.

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Figures

Figure 1
Figure 1
Gene set enrichment analysis and hierarchical clustering of microRNA expression in Alzheimer BMC. (A) The significantly upregulated miRNA in AD are ranked in order of significance from top to bottom. (B) The hierarchical clustering of subjects was determined using Pearson correlation.
Figure 2
Figure 2
Quantitative real time PCR of miRNA levels in AD. Fold differences in miRNA levels between NEC and AD were estimated by the delta Ct method.
Figure 3
Figure 3
Functional categories of predicted microRNA targets downregulated in Alzheimer BMC. Targets of upregulated BMC miRNA were compared to previous downregulated mRNA data in Alzheimer BMC (Maes et al. 2006), and summarized according to percentage of targets per functional category. The average number of miRNAs targeting the same gene within each category is reported.
See this image and copyright information in PMC

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