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. 2020 Dec 14;21(24):9500.
doi: 10.3390/ijms21249500.

Alzheimer's, Parkinson's Disease and Amyotrophic Lateral Sclerosis Gene Expression Patterns Divergence Reveals Different Grade of RNA Metabolism Involvement

Maria Garofalo  1   2 , Cecilia Pandini  1 , Matteo Bordoni  3 , Orietta Pansarasa  1 , Federica Rey  4   5 , Alfredo Costa  6   7 , Brigida Minafra  8 , Luca Diamanti  9 , Susanna Zucca  1   10 , Stephana Carelli  4   5 , Cristina Cereda  1 , Stella Gagliardi  1
Affiliations

Alzheimer's, Parkinson's Disease and Amyotrophic Lateral Sclerosis Gene Expression Patterns Divergence Reveals Different Grade of RNA Metabolism Involvement

Maria Garofalo et al. Int J Mol Sci. .

Abstract

Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) are neurodegenerative disorders characterized by a progressive degeneration of the central or peripheral nervous systems. A central role of the RNA metabolism has emerged in these diseases, concerning mRNAs processing and non-coding RNAs biogenesis. We aimed to identify possible common grounds or differences in the dysregulated pathways of AD, PD, and ALS. To do so, we performed RNA-seq analysis to investigate the deregulation of both coding and long non-coding RNAs (lncRNAs) in ALS, AD, and PD patients and controls (CTRL) in peripheral blood mononuclear cells (PBMCs). A total of 293 differentially expressed (DE) lncRNAs and 87 mRNAs were found in ALS patients. In AD patients a total of 23 DE genes emerged, 19 protein coding genes and four lncRNAs. Through Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses, we found common affected pathways and biological processes in ALS and AD. In PD patients only five genes were found to be DE. Our data brought to light the importance of lncRNAs and mRNAs regulation in three principal neurodegenerative disorders, offering starting points for new investigations on deregulated pathogenic mechanisms.

Keywords: Alzheimer’s disease; Parkinson’s disease; amyotrophic lateral sclerosis; gene expression; long non-coding RNAs.

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Conflict of interest statement

The authors declare no conflict of interest. S.Z. has shares of enGenome, an italian bioinformatics company The funders and enGenome had no role in the design of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Expression profiles of differently expressed genes in SALS, AD, PD and healthy controls. In panel (A), SALS differentially expressed mRNAs are shown, while in panel (B) SALS differentially expressed lncRNAs are shown. 10 sALS and 3 CTRLs were used for this analysis. In panel (C) and (D) both mRNAs and lncRNAs DE respectively in AD and PD are shown, given the lower amount of DE genes. For both AD and PD heatmaps, 6 patients’ samples and 6 CTRLs were used. All comparisons are given between the disease state and the control samples. We considered as differentially expressed only genes showing |log2(disease sample/healthy donor)| ≥ 1 and a False Discovery Rate ≤ 0.1.
Figure 2
Figure 2
Differentially expressed transcripts verified by Real Time PCR in PBMCs from a larger cohort of SALS and CTRLs (N = 30 for lncRNAs and N = 10 for coding RNAs. * p < 0.05, ** p < 0.001 vs. CTR).
Figure 3
Figure 3
Differentially expressed transcripts verified by Real Time PCR in PBMC from AD and CTRs (N = 6).
Figure 4
Figure 4
Differentially expressed transcripts verified by Real Time PCR in PBMC from PD and CTRs (N = 6).
Figure 5
Figure 5
Analysis of pathways performed with KEGG using DE genes in SALS group compared to healthy controls. We only show top 10 KEGG terms. The significance of the specific gene-set term is represented by the length of the bar. The significance of the term is indicated by the brightness of the bar’s color (the brighter, the more significant).
Figure 6
Figure 6
GO analysis for DE genes in SALS patients compared to healthy controls. TOP10 enriched GO terms for biological process (A), molecular function (B) and cellular component (C) The length of the bar represents the significance of that specific gene-set or term. The brighter the color, the more significant that term is, and the grey color refers to non-significant terms.
Figure 7
Figure 7
Pathways analysis performed with KEGG using DE genes in AD group compared to healthy controls. We report the top 10 KEGG terms. The significance of the specific gene-set term is represented by the length of the bar. The significance of the term is indicated by the brightness of the bar’s color (the brighter, the more significant).
Figure 8
Figure 8
Biological process (A), molecular function (B) and cellular component (C) enrichment analysis performed on DE genes in AD patients compared to healthy controls. The significance of the specific gene-set term is represented by the length of the bar. The significance of the term is indicated by the brightness of the bar’s color (the brighter, the more significant).
Figure 9
Figure 9
Venn diagram shows differentially expressed genes in common among the three conditions. No common deregulated gene emerged from DE analysis. In red the number of DE genes in SALS, in yellow the number of DE genes on AD and in green the number of DE genes in PD.
See this image and copyright information in PMC

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