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.
Highlights
Alzheimer disease (AD) is the most prevalent dementia [1]
The aim of this work was to carry out the integration of epigenomics and lipidomics analysis in plasma samples from patients with mild cognitive impairment (MCI) due to Alzheimer Disease (AD), in order to advance the knowledge of early physiopathological mechanisms
The integration of omics results helps to give a global image of the mechanisms involved in complex diseases [28]
Summary
Alzheimer disease (AD) is the most prevalent dementia [1]. Some hallmarks are clearly related to AD; accumulation of extracellular β-amyloid plaques and intracellularTau neurofibrillary tangles. AD development could involve the reconfiguration of the epigenome and the modification of some genes expression have an impact in different disease pathways [3]. Differential expression of microRNAs have been found in recent AD studies [4,5] These miRNAs could act as an epigenetic mechanism modifying the expression of different proteins post-transcriptionally [6]. An increase or decrease in the levels of miRNAs could influence the expression of different proteins or enzymes In this context, Hébert et al. Alzheimer Disease (AD) is the most prevalent dementia. The physiopathological mechanisms involved in its development are unclear In this sense, a multiomics approach could provide some progress. 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. 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
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