Key gene network related to primary ciliary dyskinesia in hippocampus of patients with Alzheimer's disease revealed by weighted gene co-expression network analysis

BMC Neurol. 2022 May 30;22(1):198. doi: 10.1186/s12883-022-02724-z.

Abstract

Background: Alzheimer's disease (AD) is closely related to aging, showing an increasing incidence rate for years. As one of the main brain regions involved in AD, hippocampus has been extensively studied due to its association with many human diseases. However, little is known about its association with primary ciliary dyskinesia (PCD).

Material and methods: The microarray data of hippocampus on AD were retrieved from the Gene Expression Omnibus (GEO) database to construct the co-expression network by weighted gene co-expression network analysis (WGCNA). The gene network modules associated with AD screened with the common genes were further annotated based on Gene Ontology (GO) database and enriched based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. The protein-protein interaction (PPI) network was constructed based on STRING database to identify the hub genes in the network.

Results: Genes involved in PCD were identified in the hippocampus of AD patients. Functional analysis revealed that these genes were mainly enriched in ciliary tissue, ciliary assembly, axoneme assembly, ciliary movement, microtubule based process, microtubule based movement, organelle assembly, axoneme dynamin complex, cell projection tissue, and microtubule cytoskeleton tissue. A total of 20 central genes, e.g., DYNLRB2, ZMYND10, DRC1, DNAH5, WDR16, TTC25, and ARMC4 were identified as hub genes related to PCD in hippocampus of AD patients.

Conclusion: Our study demonstrated that AD and PCD have common metabolic pathways. These common pathways provide novel evidence for further investigation of the pathophysiological mechanism and the hub genes suggest new therapeutic targets for the diagnosis and treatment of AD and PCD.

Subjects: Bioinformatics, Cell Biology, Molecular Biology, Neurology.

Keywords: Alzheimer’s disease; Functional enrichment analysis; Primary ciliary dyskinesia; Protein-protein interaction network; WGCNA; hub gene.

MeSH terms

  • Alzheimer Disease* / genetics
  • Ciliary Motility Disorders*
  • Gene Expression Profiling
  • Gene Regulatory Networks / genetics
  • Hippocampus
  • Humans