Transcriptional Profiling of Hippocampus Identifies Network Alterations in Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by rapid brain cell degeneration affecting different areas of the brain. Hippocampus is one of the earliest involved brain regions in the disease. Modern technologies based on high-throughput data have identified transcriptional profiling of several neurological diseases, including AD, for a better comprehension of genetic mechanisms of the disease. In this study, we investigated differentially expressed genes (DEGs) from six Gene Expression Omnibus (GEO) datasets of hippocampus of AD patients. The identified DEGs were submitted to Weighted correlation network analysis (WGCNA) and ClueGo to explore genes with a higher degree centrality and to comprehend their biological role. Subsequently, MCODE was used to identify subnetworks of interconnected DEGs. Our study found 40 down-regulated genes and 36 up-regulated genes as consensus DEGs. Analysis of the co-expression network revealed ACOT7, ATP8A2, CDC42, GAD1, GOT1, INA, NCALD, and WWTR1 to be genes with a higher degree centrality. ClueGO revealed the pathways that were mainly enriched, such as clathrin coat assembly, synaptic vesicle endocytosis, and DNA damage response signal transduction by p53 class mediator. In addition, we found a subnetwork of 12 interconnected genes (AMPH, CA10, CALY, NEFL, SNAP25, SNAP91, SNCB, STMN2, SV2B, SYN2, SYT1, and SYT13). Only CA10 and CALY are targets of known drugs while the others could be potential novel drug targets.

MIAMI-AD (Methylation in Aging and Methylation in AD): an integrative knowledgebase that facilitates explorations of DNA methylation across sex, aging, and Alzheimer’s disease

“…These results are supported by another study that found decreased CACNG2 gene expression levels in the prefrontal cortex of schizophrenia patients [66]. In AD, consistent with our observed hypomethylation at the CACNG2 gene body [30], another study also noted decreased CACNG2 gene expression in the hippocampus of AD patients [67].…”

From genetic correlations of Alzheimer’s disease to classification with artificial neural network models

“…Five publicly available datasets of gene expression profiles of Alzheimer patients (GSE1297, GSE5281, GSE36980, GSE29378, and GSE48350) were downloaded from the Gene Expression Omnibus (GEO). These datasets contain the gene expression profiles of hippocampus of Alzheimer patients as this brain area is involved in the early stages of disease (Quarato et al 2022 ). We considered hippocampus because we suppose that this part of brain plays a fundamental role in different traits associated with AD.…”