GENOME-WIDE MICRORNA AND MRNA EXPRESSION PATTERN IN ALZHEIMER’S DISEASE

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs that are involved in multiple biological and cellular processes by post-transcriptional regulation of gene expression. Dysregulation of miRNAs have been associated with various disorders, including neurodegenerative diseases such as Alzheimer's disease (AD). Most miRNA studies in AD so far were hypothesis-driven candidate-driven approaches using limited sample sizes and/or lack of independent replications. This study aims at the simultaneous investigation of genome wide miRNA and mRNA expression patterns of cortical whole-brain tissues in AD patients and healthy controls. To characterize the AD miRNA signature we examined genome-wide miRNA (> 1200) and mRNA expression patterns in the temporal cortex (TC) of 64 AD and control samples provided by the Munich Brain Bank. We validated our miRNA results by semi-quantitative real time PCR in independent brain samples using prefrontal cortex (PFC) provided by the Netherland Brain bank. Further, we separated grey and white matter brain sections to identify the cellular origin of the altered miRNA expression. Significantly deregulated miRNAs and mRNAs were correlated and examined for potential binding sites (in silico). We observed genome-wide down-regulation 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. Correlation and binding site analyses revealed several potential target genes. This miRNome-wide study in AD brains provides supportive evidence to previous studies and corroborates an important contribution of miR-132/212 and corresponding target mRNAs to the pathogenesis of AD.