Epigenomics and Lipidomics Integration in Alzheimer Disease: Pathways Involved in Early Stages

Abstract

Background: Alzheimer Disease (AD) is the most prevalent dementia. However, the physiopathological mechanisms involved in its development are unclear. In this sense, a multi-omics approach could provide some progress. Methods: Epigenomic and lipidomic analysis were carried out in plasma samples from patients with mild cognitive impairment (MCI) due to AD (n = 22), and healthy controls (n = 5). Then, omics integration between microRNAs (miRNAs) and lipids was performed by Sparse Partial Least Squares (s-PLS) regression and target genes for the selected miRNAs were identified. Results: 25 miRNAs and 25 lipids with higher loadings in the sPLS regression were selected. Lipids from phosphatidylethanolamines (PE), lysophosphatidylcholines (LPC), ceramides, phosphatidylcholines (PC), triglycerides (TG) and several long chain fatty acids families were identified as differentially expressed in AD. Among them, several fatty acids showed strong positive correlations with miRNAs studied. In fact, these miRNAs regulated genes implied in fatty acids metabolism, as elongation of very long-chain fatty acids (ELOVL), and fatty acid desaturases (FADs). Conclusions: The lipidomic–epigenomic integration showed that several lipids and miRNAs were differentially expressed in AD, being the fatty acids mechanisms potentially involved in the disease development. However, further work about targeted analysis should be carried out in a larger cohort, in order to validate these preliminary results and study the proposed pathways in detail.