Differential Expression and miRNA-Gene Interactions in Early and Late Mild Cognitive Impairment.
Leonardo Miranda BritoÂndrea Ribeiro-Dos-SantosAmanda Ferreira VidalGilderlanio Santana de AraújoPublished in: Biology (2020)
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 with limma package 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 and edgeR (FDR p-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.
Keyphrases
- mild cognitive impairment
- rna seq
- cognitive decline
- single cell
- genome wide identification
- genome wide
- end stage renal disease
- electronic health record
- transcription factor
- newly diagnosed
- chronic kidney disease
- big data
- dna methylation
- ejection fraction
- bioinformatics analysis
- prognostic factors
- copy number
- peritoneal dialysis
- healthcare
- high throughput
- early onset
- patient reported outcomes
- small molecule
- high fat diet
- insulin resistance
- case control
- patient reported
- skeletal muscle
- protein protein