Exploration of plasma lipids in mild cognitive impairment due to Alzheimer's disease

Abstract

<p><i>Background: </i>Lipids have important structural roles in cell membranes and changes to these membrane lipids may influence β- and γ-secretase activities and thus contribute to Alzheimer’s disease (AD) pathology. <p><i>Objective:</i> To explore baseline plasma lipid profiling in participants with mild cognitive impairment (MCI) with and without AD pathology. <p><i>Methods: </i>We identified 261 plasma lipids using reversed-phase liquid chromatography/mass spectrometry in cerebrospinal fluid amyloid positive (Aβ+) or negative (Aβ–) participants with MCI as compared to controls. Additionally, we analyzed the potential associations of plasma lipid profiles with performance on neuropsychological tests at baseline and after two years. <p><i>Results: </i>Sphingomyelin (SM) concentrations, particularly, SM(d43:2), were lower in MCI Aβ+ individuals compared to controls. Further, SM(d43:2) was also nominally reduced in MCI Aβ+ individuals compared to MCI Aβ–. No plasma lipids were associated with performance on primary neuropsychological tests at baseline or between the two time points after correction for multiple testing. <p><i>Conclusion: </i>Reduced plasma concentrations of SM were associated with AD.