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Identification of Phospholipid Species Implicated in Dementia by Untargeted High Resolution LC/MS and Data Dependent MS/MS

Reputable Mentor II
Reputable Mentor II
David A Peake1, Mandy Bowman1, Reiko Kiyonami1 and Danni Li2

Alzheimer’s disease (AD) is the leading cause of dementia in the elderly. Recently, Mapstone et al.1 reported a panel of plasma phospholipids (Table 1) that predicted cognitively normal adults who later progressed to either mild cognitive impairment or dementia due to AD. This study utilized a targeted metabolomics p180 kit (Biocrates, Life Science AG, Austria) that measures phospholipids by infusion and selected reaction monitoring (SRM) with a triple quadrupole mass spectrometer. Since phospholipids have many isomers and isobars comprised of different fatty acid and alkyl/alkenyl ether combinations, it is not possible to assign unequivocally the phospholipid species using a low resolution approach. Identification of fatty acid constituents in phospholipids implicated in AD is critical for two reasons: (a) to determine the functions of these lipids and their contributions to the pathophysiology of disease; and (b) to determine the molecular identities so one can develop quantitative assays to measure these particular phospholipids in human plasma. The objective of this study is to determine which fatty acids comprise phosphatidylcholine (PC) lipids including lyso-PC 18:2; PC 36:6, 38:0, 38:6, 40:1, 40:2, 40:6 and 40:6e (ether) in human plasma using liquid chromatography and high-resolution accurate mass and tandem mass spectrometry (LC-MS/MS). These results demonstrate that high resolution accurate mass (HRAM) LC-MS/MS is an excellent method for identifying isomeric lipid species from human plasma and which is essential for discovering the most meaningful changes between normal and diseased states.

1. Thermo Fisher Scientific, 355 River Oaks Parkway, San Jose, CA, USA 95134 2. University of Minnesota Medical Center, 420 Delaware Street SE, Minneapolis, MN, USA 55455
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‎10-15-2021 11:38 AM
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