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

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. Electronic supplementary material The online version of this article (10.1186/s13041-019-0436-5) contains supplementary material, which is available to authorized users.

Transcriptomic signatures of brain regional vulnerability to Parkinson’s disease

“…This loss may result from a downregulation of genes within M47 in the substantia nigra of PD patients, similarly as was observed in blood transcriptomics of PD [38][39][40] . This could be confirmed for ATXN3 in the substantia nigra of PD patients 42 . Therefore, these genes have the potential to serve as blood biomarkers for PD vulnerability.…”

A new synuclein-transgenic mouse model for early Parkinson’s reveals molecular features of preclinical disease

“…In a fourth relevance assessment step, to test the relevance of the mouse model to study molecular events leading to an early-PD like phenotype, the human orthologues of the lists of DEGs between genotypes (HET versus WT) obtained from the mouse data for each age (3M, 9M, 13M) were compared to the list of DEGs from a recent meta-analysis of transcriptomics data from post-mortem brain samples of PD patients and controls conducted by Kelly et al [48]. Thus, with these 4 relevance assessment steps, we evaluated whether the mouse model data can provide an adequate reflection of the alterations associated with early PD progression.…”

“…When comparing the DEGs obtained in this study to the list of DEGs from a meta-analysis of transcriptomics data from post-mortem brain samples from the SN midbrain region from a previous study [48], we observed a significant overlap with the DEGs between genotypes (HET versus WT) for 3 months old mice (45 genes, Fisher's exact test p-value = 0.003, see Table S7), but no overlap with the 5 DEGs obtained for 9 months old mice.…”

A New Synuclein-Transgenic Mouse Model for Early Parkinson’s Reveals Molecular Features of Preclinical Disease

“…When comparing the DEGs obtained in this study to the list of DEGs from a meta-analysis of transcriptomics data from post-mortem brain samples from the SN midbrain region from a previous study [61], we observed a significant overlap with the DEGs between genotypes (HET versus WT) for 3-month-old mice (45 genes, Fisher's exact test p value = 0.003, see Table S7), but no overlap with the 5 DEGs obtained for 9-month-old mice. Furthermore, also the higher level analyses of molecular pathways and GO terms point to cellular processes that match with previously proposed mechanisms associated with PD (see previous sections).…”