Dysregulated gene-associated biomarkers for Alzheimer's disease and aging

Abstract

Alzheimer's disease (AD), the most common type of dementia, is a neurodegenerative disorder with a hidden onset, including difficult early detection and diagnosis. Nevertheless, the new crucial biomarkers for the diagnosis and pathogenesis of AD need to be explored further. Here, the common differentially expressed genes (DEGs) were identified through a comprehensive analysis of gene expression profiles from the Gene Expression Omnibus (GEO) database. Furthermore, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that these DEGs were mainly associated with biological processes, cellular components, and molecular functions, which are involved in multiple cellular functions. Next, we found that 9 of the 24 genes showed the same regulatory changes in the blood of patients with AD compared to those in the GEO database, and 2 of the 24 genes showed a significant correlation with Montreal Cognitive Assessment scores. Finally, we determined that mice with AD and elderly mice had the same regulatory changes in the identified DEGs in both the blood and hippocampus. Our study identified several potential core biomarkers of AD and aging, which could contribute to the early detection, differential diagnosis, treatment, and pathological analysis of AD.

Keywords: Alzheimer’s disease; aging; blood; differentially expressed genes; hippocampus.

Figure 1

Analysis of differentially expressed genes in AD patients’ blood samples. (a) The framework of the whole study design. (b) The common DEGs derived from the Venn analysis of the three expression profiles (GSE4226, GSE4227, and GSE4229). (c) Expression levels of the common 24 DEGs in AD blood samples. The red column represents upregulated DEGs, and the blue column represents downregulated DEGs. (d) GO and KEGG pathway analyses of the DEGs.

Figure 2

The age, sex, and MoCA scores of the patients. (a) Age, (b) sex, and (c) MoCA scores of patients with NECs and AD. NECs: n = 21; AD: n = 20. ***p < 0.001 compared to control subjects.

Figure 3

Detection of DEGs in the blood samples of patients with AD. (a) Significant changes in gene expression in line with the GSE data, (b) significant changes in gene expression in direct contrast to those in the GSE data analysis, (c) no changes in gene expression. NECs: n = 21; AD: n = 20. *p < 0.05; **p < 0.01; ***p < 0.001 compared to normal.

Figure 4

Correlation analysis of the nine identified DEGs with MoCA scores. (a) The genes showing significant positive correlation with MoCA scores. (b) The genes showing no significant correlation with the MoCA scores.

Figure 5

The mRNA expression levels of the nine identified DEGs in AD mice. The mRNA expression levels of the nine identified DEGs in the blood (a) and hippocampi (b). WT mice, n = 11; AD mice, n = 12; *p < 0.05; **p < 0.01; ***p < 0.001 compared to WT.

Figure 6

The mRNA expression levels of the nine identified DEGs in aging mice. Morris Water Maze (a) and Y-Maze tests (b) of 2- and 24-month-old mice. The mRNA expression levels of the nine identified DEGs in the blood (c) and hippocampi (d). 2 months, n = 10; 24 months, n = 9. *p < 0.05, **p < 0.01, ***p < 0.001 compared to 2 months.