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.
Highlights
Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease (ND) effecting approximately 145,000 people in the UK [1]
Data sets collected for this study Our search criteria found 7 Affymetrix chip datasets which included 69 PD and 57 control samples
Information about the datasets is shown in Additional file 1: Table S1
Summary
Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease (ND) effecting approximately 145,000 people in the UK [1]. It is predicted that the number of PD patients in the UK will increase by 18.1% between 2015 and 2065 [1]. In the US it is predicted that PD cases will increase from 680,000 to 1,238,000 by 2030 [2]. PD primarily affects motor systems of the central nervous system because of the death of dopamine generating cells in the substantia nigra (SN) in the midbrain [3]. Alzheimer’s disease (AD) is the most common ND accounting for 60–80% of dementia cases, characterised pathologically by deposits of intracellular tau neurofibrillary tangles and accumulation of extracellular amyloid β (Aβ) plaques in the brain [4]. The most common clinical symptom of AD is gradual progressive memory loss that eventually affects other cognitive functions such as communication and movement. There are currently many promising advances in the understanding of AD, including novel biomarkers [5, 6] and underlying biological mechanisms [7]
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