Expression Profiling and Pathway Analysis of Long Non-Coding RNAs as drivers of Alzheimer’s Disease Pathology

Abstract

Alzheimer’s disease is a progressive multi-factorial neurodegenerative disease characterized by cognitive decline and synaptic loss and is one of the most prominent healthcare challenges of this century. Technology advances and research has identified a number of therapeutic biomarkers to understand Alzheimer’s disease, however, all proposed therapeutic strategies are symptomatic with no significant effect on treatment of the disease. Global research community dedicated to investigate dementia and neurodegenerative diseases is on a continuous quest to map the correct pathological events and find targets to halt the disease progression. Mounting evidence of the regulatory effect of non-coding genome in various diseases has opened new avenues of diagnostic and therapeutic biomarker research. In this study, we highlight the important long non-coding RNAs as potential biomarkers of Alzheimer’s disease through integrated bioinformatics analysis of publicly available datasets. We have reported the important genes and punctuated their role in various biological pathways and processes through extensive enrichment analysis studies. BAIAP3 and TAMALIN are the two differentially expressed genes that were common between all datasets under this study. These genes are involved in neuronal differentiation and survival and important regulators of synaptic transmission and neurotransmitter transport and secretion. MEG3, NEAT1, SOX2-OT and BAALC-AS are the most significant differentially expressed long non-coding RNAs that regulate the neuroinflammation, oxidative stress, amyloid metabolism and apoptosis related pathways. CHRM1, AKAP10, NCALS, RPRD2, ATXN1 and TRIO are identified as the important target genes of long non-coding RNA transcripts that were found to be enriched in synaptic signaling and neurotransmission. Our multi-dataset analysis provides a comprehensive overview of RNA expression in Alzheimer’s disease, shedding light on the intricate interplay between protein-coding genes and lncRNAs in disease pathology