Identification of Alzheimer's disease-associated long noncoding RNAs

Abstract

Alzheimer's disease (AD) is the most common dementia among the elderly that involves complex neurodegenerative alterations. Multiple cellular processes including regulation of amyloid-β peptide, tau, inflammation, and cell death have been suggested to associate with AD, but it remains largely unknown if long noncoding RNAs (lncRNAs) may be playing a role in AD pathogenesis. Here, we identify AD-associated lncRNAs by reannotation of microarray data based on postmortem tissue samples of AD patients and matched elderly controls. We found 24 upregulated and 84 downregulated lncRNAs in AD patients compared with controls, most being intergenic. An analysis of lncRNAs in various tissues indicated that most downregulated lncRNAs in AD are highly expressed in the brain but not in other tissues. Gene set enrichment analysis identified a downregulated lncRNA n341006 in association with protein ubiquitination pathway, and a significantly upregulated lncRNA n336934 linked to cholesterol homeostasis. Interestingly, lncRNA expression signatures could predict tissue types with equal accuracy as protein-coding genes, but the number of lncRNAs required for optimal prediction was less than protein-coding genes. Taken together, our study provides a resource for AD-associated lncRNAs for the development of lncRNA biomarkers and the identification of functional lncRNAs involved in AD pathogenesis.