Evaluation of the regulatory mechanisms underlying genetic differentiation is necessary to better understand the neurobiology of AD [13]. Transcriptional and translation regulation by microRNAs (miRNAs) in substance use disorders and AD is a growing field of interest in recent years [14]. MiRNAs are small, non-coding, regulatory RNA molecules that function primarily to repress translation of an estimated 30–50% of all protein-coding genes by downregulation of mRNA [15]. MiRNA play a pivotal role in regulation of the central nervous system (CNS), where approximately 70% of known miRNAs are expressed. Similarly, mRNA in the CNS have longer 3’ untranslated regions (3’ UTRs), which represent a large number of potential miRNA target sites [16, 17]. The cooperative and combinatorial targeting ability of miRNA allow precise and robust gene regulation at both the single-gene and the gene-network level [18]. To date, there have been limited studies in rodent and cell-based models, and even fewer studies of genome-wide miRNA expression in AD postmortem brain tissue [19–23]. One such study on the PFC of AD subjects identified 35 upregulated miRNAs, which are known to target mRNAs
