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. 2021 Mar;246(5):584-595.
doi: 10.1177/1535370220967325. Epub 2020 Nov 4.

Transcriptomic profiles in Parkinson's disease

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Transcriptomic profiles in Parkinson's disease

Lille Kurvits et al. Exp Biol Med (Maywood). 2021 Mar.

Abstract

Transcriptomics in Parkinson's disease offers insights into the pathogenesis of Parkinson's disease but obtaining brain tissue has limitations. In order to bypass this issue, we profile and compare differentially expressed genes and enriched pathways (KEGG) in two peripheral tissues (blood and skin) of 12 Parkinson's disease patients and 12 healthy controls using RNA-sequencing technique and validation with RT-qPCR. Furthermore, we compare our results to previous Parkinson's disease post mortem brain tissue and blood results using the robust rank aggregation method. The results show no overlapping differentially expressed genes or enriched pathways in blood vs. skin in our sample sets (25 vs. 1068 differentially expressed genes with an FDR ≤ 0.05; 1 vs. 9 pathways in blood and skin, respectively). A meta-analysis from previous transcriptomic sample sets using either microarrays or RNA-Seq yields a robust rank aggregation list of cortical gene expression changes with 43 differentially expressed genes; a list of substantia nigra changes with 2 differentially expressed genes and a list of blood changes with 1 differentially expressed gene being statistically significant at FDR ≤ 0.05. In cortex 1, KEGG pathway was enriched, four in substantia nigra and two in blood. None of the differentially expressed genes or pathways overlap between these tissues. When comparing our previously published skin transcription analysis, two differentially expressed genes between the cortex robust rank aggregation and skin overlap. In this study, for the first time a meta-analysis is applied on transcriptomic sample sets in Parkinson's disease. Simultaneously, it explores the notion that Parkinson's disease is not just a neuronal tissue disease by exploring peripheral tissues. The comparison of different Parkinson's disease tissues yields surprisingly few significant differentially expressed genes and pathways, suggesting that divergent gene expression profiles in distinct cell lineages, metabolic and possibly iatrogenic effects create too much transcriptomic noise for detecting significant signal. On the other hand, there are signs that point towards Parkinson's disease-specific changes in non-neuronal peripheral tissues in Parkinson's disease, indicating that Parkinson's disease might be a multisystem disorder.

Keywords: Biomarkers; blood; brain; neurodegeneration; skin; transcriptomics.

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Conflict of interest statement

Declaration OF CONFLICTING INTERESTS: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
A schematic comparison of the original RNA-Seq data from Parkinson’s disease blood and skin samples visualizing the differences in number of DEGs and KEGG pathways and showing no overlap.
Figure 2.
Figure 2.
A schematic overview of previously published cortex and substantia nigra RNA-Seq and microarray studies showing the number DEGs in each single study, overlapping DEGs and KEGG pathways in the RRA analysis.
Figure 3.
Figure 3.
A schematic overview of the studies involved in RRA analysis (51/39 is the number of Parkinson’s disease patients and healthy controls in the original study respectively), the output DEGs and KEGG pathways, and the overlap between the investigated studies.

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