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 dysregul...

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Published in:Biology (Basel, Switzerland) Switzerland), 2020-09, Vol.9 (9), p.251
Main Authors: Brito, Leonardo Miranda, Ribeiro-dos-Santos, Andrea, Vidal, Amanda Ferreira, Araujo, Gilderlanio Santana de
Format: Article
Language:English
Subjects:
Alzheimer's disease
Amyloid precursor protein
Apolipoprotein E
Biomarkers
Brain
Cognitive ability
Dementia
Dementia disorders
Disease
DNA methylation
DNA microarrays
Gene expression
genes
Genetic aspects
Genetic research
Health aspects
MicroRNA
MicroRNAs
mild cognitive impairment
miRNA
miRNAs
Neurodegeneration
Neurodegenerative diseases
Presenilin 1
Proteins
Psychological research
regulatory interactions
Regulatory sequences
RNA sequencing
Transcriptomics
Transient receptor potential proteins
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Summary: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.
ISSN:2079-7737
2079-7737
DOI:10.3390/biology9090251