Increased Lysophosphatidyleth-anolamine and Diacylglycerol levels in Alzheimer’s Disease Plasma

Abstract

Background: Previous studies have demonstrated deficits in biosynthesis of plasmalogens and sphingolipids in Alzheimer ’s Disease (AD). Objective: We undertook an analysis of alternate biomarkers of lipid synthesis, metabolism, and remodeling “Lands” cycle in the plasma of control and cognitively impaired patients based upon their Mini-Mental State Examination (MMSE) scores. Methods: Plasma levels of 600 lipids were measured utilizing a high-resolution mass spectrometric shotgun analysis platform. Results: The lyso metabolites of phosphatidylethanolamines and phosphatidylglycerols, along with diacyglycerols were all elevated in the plasma of patients with cognitive impairment.There were no significant differences in the plasma levels of fatty acids metabolized by peroxisomes. Conclusion: The increased levels of lysolipids and diacylglycerols in theplasma of all patient groups suggest that lipid remodeling is dysfunctional early in the AD disease process. It remains to be determined if this involves increased phospholipase A2 activity, decreased acyltransferase activity, or decreased cellular uptake of lysophospholipids for subsequent acylation.