Exploration of Plasma Lipids in Mild Cognitive Impairment due to Alzheimer's Disease.

BACKGROUND 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. OBJECTIVE To explore baseline plasma lipid profiling in participants with mild cognitive impairment (MCI) with and without AD pathology. METHODS We analyzed 261 plasma lipid profiles using reversed phase 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. RESULTS 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 neuropsychological tests at baseline or between the two time points after correction for multiple testing. CONCLUSION Reduced plasma concentrations of SM were associated with AD.