title: 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.
authors.affiliation: Molecular Neurology Program, Huntington Medical Research Institutes, Pasadena, CA 91101-1830.
authors.forename: Alfred N
authors.initials: AN
authors.lastname: Fonteh
authors.forename: Jiarong
authors.initials: J
authors.lastname: Chiang
authors.forename: Matthew
authors.initials: M
authors.lastname: Cipolla
authors.forename: Jack
authors.initials: J
authors.lastname: Hale
authors.forename: Fatimatou
authors.initials: F
authors.lastname: Diallo
authors.forename: Alejandra
authors.initials: A
authors.lastname: Chirino
authors.forename: Xianghong
authors.initials: X
authors.lastname: Arakaki
authors.forename: Michael G
authors.initials: MG
authors.lastname: Harrington
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000201:enzymology / Q000473:pathology; D005260:Female; D020404:Glycerophospholipids / Q000134:cerebrospinal fluid* / Q000302:isolation & purification; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D054467:Phospholipases A2 / Q000134:cerebrospinal fluid*; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry
chemical_list: D020404:Glycerophospholipids; D054467:Phospholipases A2
keywords: lipid metabolism; liquid chromatography; mass spectrometry; minimal cognitive impairment; nanoparticles; neurodegeneration