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Alterations in cerebrospinal fluid glycerophospholipids and phospholipase A2 activity in Alzheimer's disease.

Abstract
Our aim is to study selected cerebrospinal fluid (CSF) glycerophospholipids (GP) that are important in brain pathophysiology. We recruited cognitively healthy (CH), minimally cognitively impaired (MCI), and late onset Alzheimer's disease (LOAD) study participants and collected their CSF. After fractionation into nanometer particles (NP) and supernatant fluids (SF), we studied the lipid composition of these compartments. LC-MS/MS studies reveal that both CSF fractions from CH subjects have N-acyl phosphatidylethanolamine, 1-radyl-2-acyl-sn-glycerophosphoethanolamine (PE), 1-radyl-2-acyl-sn-glycerophosphocholine (PC), 1,2-diacyl-sn-glycerophosphoserine (PS), platelet-activating factor-like lipids, and lysophosphatidylcholine (LPC). In the NP fraction, GPs are enriched with a mixture of saturated, monounsaturated, and polyunsaturated fatty acid species, while PE and PS in the SF fractions are enriched with PUFA-containing molecular species. PC, PE, and PS levels in CSF fractions decrease progressively in participants from CH to MCI, and then to LOAD. Whereas most PC species decrease equally in LOAD, plasmalogen species account for most of the decrease in PE. A significant increase in the LPC-to-PC ratio and PLA2 activity accompanies the GP decrease in LOAD. These studies reveal that CSF supernatant fluid and nanometer particles have different GP composition, and that PLA2 activity accounts for altered GPs in these fractions as neurodegeneration progresses.
AuthorsAlfred N Fonteh, Jiarong Chiang, Matthew Cipolla, Jack Hale, Fatimatou Diallo, Alejandra Chirino, Xianghong Arakaki, Michael G Harrington
JournalJournal of lipid research (J Lipid Res) Vol. 54 Issue 10 Pg. 2884-97 (Oct 2013) ISSN: 1539-7262 [Electronic] United States
PMID23868911 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Glycerophospholipids
  • Phospholipases A2
Topics
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease (cerebrospinal fluid, enzymology, pathology)
  • Female
  • Glycerophospholipids (cerebrospinal fluid, isolation & purification)
  • Humans
  • Lipid Metabolism
  • Male
  • Phospholipases A2 (cerebrospinal fluid)
  • Spectrometry, Mass, Electrospray Ionization
  • Tandem Mass Spectrometry

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