Gene expression meta-analysis of Parkinson's disease and its relationship with Alzheimer's disease

Jack Kelly, Rana Moyeed, Camille Carroll, Diego Albani, Xinzhong Li

Research output: Contribution to journalArticle

Abstract

Parkinson's disease (PD) and Alzheimer's disease (AD) are the most common neurodegenerative diseases and have been suggested to share common pathological and physiological links. Understanding the cross-talk between them could reveal potentials for the development of new strategies for early diagnosis and therapeutic intervention thus improving the quality of life of those affected. Here we have conducted a novel meta-analysis to identify differentially expressed genes (DEGs) in PD microarray datasets comprising 69 PD and 57 control brain samples which is the biggest cohort for such studies to date. Using identified DEGs, we performed pathway, upstream and protein-protein interaction analysis. We identified 1046 DEGs, of which a majority (739/1046) were downregulated in PD. YWHAZ and other genes coding 14-3-3 proteins are identified as important DEGs in signaling pathways and in protein-protein interaction networks (PPIN). Perturbed pathways also include mitochondrial dysfunction and oxidative stress. There was a significant overlap in DEGs between PD and AD, and over 99% of these were differentially expressed in the same up or down direction across the diseases. REST was identified as an upstream regulator in both diseases. Our study demonstrates that PD and AD share significant common DEGs and pathways, and identifies novel genes, pathways and upstream regulators which may be important targets for therapy in both diseases.

Original languageEnglish
Pages (from-to)16
JournalMolecular Brain
Volume12
Issue number1
DOIs
Publication statusPublished - Feb 28 2019

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Keywords

  • Alzheimer Disease/genetics
  • Down-Regulation/genetics
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Humans
  • Parkinson Disease/genetics
  • Protein Interaction Maps/genetics
  • Signal Transduction/genetics
  • Transcription, Genetic

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