Identification of key regulatory molecules in the early development stage of Alzheimer's disease

Abstract

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases, the incidence of which increases with age, and the pathological changes in the brain are irreversible. Recent studies have highlighted the essential role of long noncoding RNAs (lncRNAs) in AD by acting as competing endogenous RNAs (ceRNAs). Our aim was to construct lncRNA‐associated ceRNA regulatory networks composed of potential biomarkers for the early stage of AD. AD related datasets come from AlzData and GEO databases. The R package ‘Limma’ identifies differentially expressed genes (DEGs), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) databases for functional enrichment analysis. Protein–protein interactions (PPIs) in DEGs were constructed in the STRING database, and Cytoscape software identified DEGs. Convergent functional genomics (CFG) analysis of differentially expressed hub genes (referred to as early‐DEGs) in the brain before the development of AD pathology. The AlzData database analyses the expression levels of early‐DEGs in different nerve cells. The lncRNA‐miRNA‐mRNA regulatory network was established according to the ceRNA hypothesis. We identified four lncRNAs (XIST, NEAT1, KCNQ1OT1 and HCG18) and four miRNAs (hsa‐let‐7c‐5p, hsa‐miR‐107, hsa‐miR‐129‐2‐3p and hsa‐miR‐214‐3p) were preliminarily identified as potential biomarkers for early AD, competitively regulating Atp6v0b, Atp6v1e1 Atp6v1f and Syt1. This study indicates that NEAT1, XIST, HCG18 and KCNQ1OT1 act as ceRNAs in competitive binding with miRNAs to regulate the expression of Atp6v0b, Atp6v1e1, Atp6v1f and Syt1 before the occurrence of pathological changes in AD.