Transcriptomic differences in MSA clinical variants

Pérez Soriano, Alexandra; Arnal, Magdalena; Botta Orfila, Teresa; Giraldo, Darly; Fernández, Manel; Compta, Yaroslau; Fernández-Santiago, Ruben; Ezquerra, Mario; Tartaglia, Gian Gaetano; Martí, M. Josep; Catalan multiple system atrophy-registry (CMSAR)

doi:http://dx.doi.org/10.1038/s41598-020-66221-4

Transcriptomic differences in MSA clinical variants

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Pérez-Soriano A, Arnal Segura M, Botta-Orfila T, Giraldo D, Fernández M, Compta Y, Fernández-Santiago R, Ezquerra M, Tartaglia GG, Martí MJ; Catalan MSA Registry (CMSAR). Transcriptomic differences in MSA clinical variants. Sci Rep. 2020; 10(1):10310. DOI: 10.1038/s41598-020-66221-4

Abstract

Background: Multiple system atrophy (MSA) is a rare oligodendroglial synucleinopathy of unknown etiopathogenesis including two major clinical variants with predominant parkinsonism (MSA-P) or cerebellar dysfunction (MSA-C). Objective: To identify novel disease mechanisms we performed a blood transcriptomic study investigating differential gene expression changes and biological process alterations in MSA and its clinical subtypes. Methods: We compared the transcriptome from rigorously gender and age-balanced groups of 10 probable MSA-P, 10 probable MSA-C cases, 10 controls from the Catalan MSA Registry (CMSAR), and 10 Parkinson Disease (PD) patients. Results: Gene set enrichment analyses showed prominent positive enrichment in processes related to immunity and inflammation in all groups, and a negative enrichment in cell differentiation and development of the nervous system in both MSA-P and PD, in contrast to protein translation and processing in MSA-C. Gene set enrichment analysis using expression patterns in different brain regions as a reference also showed distinct results between the different synucleinopathies. Conclusions: In line with the two major phenotypes described in the clinic, our data suggest that gene expression and biological processes might be differentially affected in MSA-P and MSA-C. Future studies using larger sample sizes are warranted to confirm these results.