Research Paper Volume 12, Issue 6 pp 5221—5243
Genetic networks in Parkinson’s and Alzheimer’s disease
- 1 Faculty of Health: Medicine, Dentistry and Human Sciences, Plymouth University, Plymouth PL6 8BU, UK
- 2 Faculty of Science and Engineering, Plymouth University, Plymouth PL6 8BU, UK
- 3 School of Science, Engineering and Design, Teesside University, Middlesbrough TS1 3BX, UK
Received: December 12, 2019 Accepted: March 9, 2020 Published: March 23, 2020
https://doi.org/10.18632/aging.102943How to Cite
Copyright © 2020 Kelly et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Parkinson’s disease (PD) and Alzheimer’s disease (AD) are the most common neurodegenerative diseases and there is increasing evidence that they share common physiological and pathological links. Here we have conducted the largest network analysis of PD and AD based on their gene expressions in blood to date. We identified modules that were not preserved between disease and healthy control (HC) networks, and important hub genes and transcription factors (TFs) in these modules. We highlighted that the PD module not preserved in HCs was associated with insulin resistance, and HDAC6 was identified as a hub gene in this module which may have the role of influencing tau phosphorylation and autophagic flux in neurodegenerative disease. The AD module associated with regulation of lipolysis in adipocytes and neuroactive ligand-receptor interaction was not preserved in healthy and mild cognitive impairment networks and the key hubs TRPC5 and BRAP identified as potential targets for therapeutic treatments of AD. Our study demonstrated that PD and AD share common disrupted genetics and identified novel pathways, hub genes and TFs that may be new areas for mechanistic study and important targets in both diseases.
Abbreviations
PD: Parkinson’s disease; AD: Alzheimer’s disease; HC: Healthy control; TFs: Transcription factors; ND: Neurodegenerative disease; Aβ: amyloid-β1; CNS: Central nervous system; SN: Substantia nigra; DEGs: Differentially expressed genes; WGCNA: Weighted gene co-expression network analysis; MCI: Mild cognitive impairment; ADAD: AD samples from Alzheimer’s dataset; ADHC: HC samples from Alzheimer’s dataset; ADMCI: MCI samples from Alzheimer’s dataset; PDPD: PD samples from Parkinson’s dataset; PDHC: HC samples from Parkinson’s dataset; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; BC: Betweenness centrality; MM: Module membership; ENCODE: Encyclopedia of DNA Elements; ChIP: Chromatin immunoprecipitation; ChEA: ChIP enrichment analysis; SNP: Single nucleotide polymorphism; GWAS: Genome Wide Association Studies; SCAN: SNP and Copy number Annotation; miRNA: microRNA; PTEN: Phosphatase and tensin homolog; TRPC: Transient receptor potential canonical; BBB: Blood brain barrier; LATE: Limbic-predominant age-related TDP-43 encephalopathy; GEO: Gene Expression Omnibus; RMA: Robust Multiarray Average; MAD: Median absolute deviation; TOM: Topological overlap matrix.