An integrated approach to unravel a putative crosstalk network in Alzheimer’s disease and Parkinson’s disease

Abstract

Integration of multiple profiling data and construction of functional regulatory networks provide a powerful approach to uncover functional relationships and significant molecular entities from transcriptomic data, highlighting the molecular mechanisms of complex diseases. Despite having an overlap in the neuropathologies of AD and PD, the molecular entities overlapped and mechanisms behind them are less known. Here we used an integrated strategy to analyze miRNA and gene transcriptomic data to understand the role of miRNAs and genes in regulatory activities taking place in cells, and find transcriptomic signatures linking AD and PD. We preprocessed and analyzed publicly available microarray datasets and identified 97 DEGs and 21 DEmiRs that may be involved in the overlapped mechanisms between these two disorders. Among the DEGs, we found HSPA9, PGK1, SDHC, FH, DLD, YWHAZ and ACLY as the major protein-coding genes involved in the crosstalk for AD-PD pathogenesis. Further we integrated these DEGs and DEmiRs with regulatory TFs to construct an overlapped dysregulated network of AD and PD. In the network, miR-27a-3p, miR-148a-3p and miR-15a-5p were found to be the most relevant with maximum interactions, describing their significance in the potential crosstalk. We also looked into the dysregulated biological processes and pathways overlapped in AD and PD. In conclusion, we highlighted the DEGs, DEmiRs, their interactions and related pathways overlapped in AD and PD pathogenesis, also describing a potential crosstalk at molecular level. Besides, our findings can further be used for molecular studies to reveal an assured AD-PD crosstalk.