Differential Expression and miRNA-Gene Interactions in Early and Late Mild Cognitive Impairment

Mild cognitive impairment (MCI) and Alzheimer's Disease (AD) are complex diseases with their molecular architecture not elucidated.APOE, Amyloid Beta Precursor Protein (APP), and Presenilin-1 (PSEN1) are well-known genes associated with both MCI and AD. Recently, epigenetic alterations and dysregulated regulatory elements, such as microRNAs (miRNAs), have been reported associated with neurodegeneration. In this study, differential expression analysis (DEA) was performed for genes and miRNAs based on microarray and RNA-Seq data. Global gene profile of healthy individuals, early and late mild cognitive impairment (EMCI and LMCI, respectively), and AD was obtained from ADNI Cohort. miRNA global profile of healthy individuals and AD patients was extracted from public RNA-Seq data. DEA performed withlimmapackage on ADNI Cohort data highlighted eight differential expressed (DE) genes (AGER,LINC00483,MMP19,CATSPER1,ARFGAP1,GPER1,PHLPP2,TRPM2) (false discovery rate (FDR)p-value < 0.05) between EMCI and LMCI patients. Previous molecular studies showed associations between these genes with dementia and neurological-related pathways. Five dysregulated miRNAs were identified by DEA performed with RNA-Seq data andedgeR(FDRp-value < 0.002). All reported miRNAs in AD interact with the aforementioned genes. Our integrative transcriptomic analysis was able to identify a set of miRNA-gene interactions that may be involved in cognitive and neurodegeneration processes.