Serum Phosphatidylethanolamine and Lysophosphatidylethanolamine Levels Differentiate Alzheimer’s Disease from Controls and Predict Progression from Mild Cognitive Impairment

Abstract

Background: There is intense interest in the development of blood-based biomarkers, not only that can differentiate Alzheimer’s disease (AD) from controls, but that can also predict conversion from mild cognitive impairment (MCI) to AD. Serum biomarkers carry the potential advantage over imaging or spinal fluid markers both in terms of cost and invasiveness. Objective: Our objective was to measure the potential for serum lipid markers to differentiate AD from age-matched healthy controls as well as to predict conversion from MCI to AD. Methods: Using a publicly-available dataset, we examined the relationship between baseline serum levels of 349 known lipids from 16 classes of lipids to differentiate disease state as well as to predict the conversion from MCI to AD. Results: We observed that several classes of lipids (cholesteroyl ester, phosphatidylethanolamine, lysophosphatidylethanolamine, and acylcarnitine) differentiated AD from normal controls. Among these, only two classes, phosphatidylethanolamine (PE) and lysophosphatidylethanolamine (lyso-PE), predicted time to conversion from MCI to AD. Low levels of PE and high levels of lyso-PE result in two-fold faster median time to progression from MCI to AD, with hazard ratios 0.62 and 1.34, respectively. Conclusion: These data suggest that serum PE and lyso-PE may be useful biomarkers for predicting MCI to AD conversion. In addition, since PE is converted to lyso-PE by phospholipase A2, an important inflammatory mediator that is dysregulated in AD, these data suggest that the disrupted serum lipid profile here may be related to an abnormal inflammatory response early in the AD pathologic cascade.