Identification of deregulated lncRNAs in Alzheimer's disease: an integrated gene co-expression network analysis of hippocampus and fusiform gyrus RNA-seq datasets

Front Aging Neurosci. 2024 Jul 17:16:1437278. doi: 10.3389/fnagi.2024.1437278. eCollection 2024.

Abstract

Introduction: The deregulation of lncRNAs expression has been associated with neuronal damage in Alzheimer's disease (AD), but how or whether they can influence its onset is still unknown. We investigated 2 RNA-seq datasets consisting, respectively, of the hippocampal and fusiform gyrus transcriptomic profile of AD patients, matched with non-demented controls.

Methods: We performed a differential expression analysis, a gene correlation network analysis (WGCNA) and a pathway enrichment analysis of two RNA-seq datasets.

Results: We found deregulated lncRNAs in common between hippocampus and fusiform gyrus and deregulated gene groups associated to functional pathways related to neurotransmission and memory consolidation. lncRNAs, co-expressed with known AD-related coding genes, were identified from the prioritized modules of both brain regions.

Discussion: We found common deregulated lncRNAs in the AD hippocampus and fusiform gyrus, that could be considered common signatures of AD pathogenesis, providing an important source of information for understanding the molecular changes of AD.

Keywords: Alzheimer’s disease; RNA-Seq; WGCNA; differentially expressed genes; lncRNAs.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was funded by the following projects: Nutrage (CNR DBA.AD005.225), PRIN2017 (MUR 2017M9L3L8_003), MNESYS (PE_0000006) AGE-IT (PE_00000015), National Center for Gene Therapy and Drugs Based on RNA Technology—MUR (CN_00000041), Life Science Hub Regione Puglia (LSH-Puglia, T4-AN-01 H93C22000560003), INNOVA - Italian Network of Excellence for Advanced Diagnosis (PNC-EJ-2022-23683266 PNC-HLS-DA) and by ELIXIR-IT Through the Empowering Project ELIXIRNextGenIT (IR0000010).