Abstract

BACKGROUND: Alzheimer disease (AD) is a common and fatal subtype of dementia that remains a challenge to diagnose and treat. This study aimed to identify potential biomarkers that influence the prognosis of AD.

MATERIAL AND METHODS: A total of 6 gene expression profiles from the Gene Expression Omnibus (GEO) database were assessed for their potential as AD biomarkers. We identified differentially expressed genes (DEGs) using the prediction analysis for microarray (PAM) algorithm and obtained hub genes through the analysis of the protein-protein interaction (PPI) network and module analysis.

RESULTS: We identified 6 gene expression profiles from the GEO database and assessed their potential as AD biomarkers. Shared gene sets were extracted and integrated into large expression profile matrices. We identified 2514 DEGs including 68 upregulated- and 2446 downregulated genes through analysis of the limma package. We screened 379 significant DEGs including 68 upregulated and 307 downregulated genes for their ability to distinguish AD from control samples using PAM algorithm. Functional enrichment of the 379 target genes was produced from Database for Annotation, Visualization and Integrated Discovery.(DAVID) and included histone function, beta receptor signaling, cell growth, and angiogenesis. The downregulated genes were significantly enriched in MAPK signaling, synaptic signaling, neuronal apoptosis and AD associated pathways. Upon analysis of the PPI network, 32 hub genes including ENO2, CCT2, CALM2, ACACB, ATP5B, MDH1, and PP2CA were screened. Of these hub genes, NFKBIA and ACACB were upregulated and 29 genes were downregulated in AD patients.

CONCLUSIONS: We screened 379 significant DEGs as potential biomarkers of AD using PAM and obtained 32 hub genes through PPI network and module analysis. These findings reveal new potential AD biomarkers with prognostic and therapeutic value.

Keywords: Alzheimer Disease, Biological Markers, Microarray Analysis, Protein Array Analysis, Aged, Algorithms, Databases, Genetic, Down-Regulation, Gene Expression Profiling, Gene Expression Regulation, Gene Regulatory Networks, Molecular Sequence Annotation, Protein Interaction Maps, Reproducibility of Results, Transcription Factors