title: Reduction of brain lipid peroxidation by CSF drainage in Alzheimer's disease patients.
abstract: Alzheimer's disease (AD) is associated with an increase in cerebrospinal fluid (CSF) levels of the isoprostane 8,12-iso-iPF2alpha-VI, a specific marker of in vivo lipid peroxidation. Poor cerebral clearance of end products of oxidative reactions via CSF circulation may contribute to and sustain ongoing stress. CSF drainage via a low-flow ventriculoperitoneal (VP) shunt may improve removal of these products, reducing oxidative stress. We quantified this biomarker in patients with AD undergoing to VP shunt placement at baseline and after one-year period. CSF sampling occurred at baseline and quarterly visits for one year. Levels of this isoprostane were determined simultaneously at the end of the study by gas chromatography negative ion chemical ionization mass spectrometry. Over one-year, CSF 8,12-iso-iPF2alpha-VI levels consistently decreased versus baseline (51% of initial level), while CSF protein, glucose, cell count and IgG concentrations remained within normal limits. This finding supports the hypothesis that improving CSF drainage enhances extra-cellular clearance of end products of oxidative reactions and lowers brain lipid peroxidation.
authors.affiliation: Department of Pharmacology, The Center for Experimental Therapeutics, University of Pennsylvania, School of Medicine, Philadelphia 19104, USA. domenico@spirit.gcrc.upenn.edu
authors.forename: Domenico
authors.initials: D
authors.lastname: Praticò
authors.forename: Yuemang
authors.initials: Y
authors.lastname: Yao
authors.forename: Joshua
authors.initials: J
authors.lastname: Rokach
authors.forename: Martha
authors.initials: M
authors.lastname: Mayo
authors.forename: Gerald G
authors.initials: GG
authors.lastname: Silverberg
authors.forename: Dawn
authors.initials: D
authors.lastname: McGuire
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000503:physiopathology / Q000601:surgery; D001921:Brain / Q000503:physiopathology*; D015170:Cerebrospinal Fluid Pressure; D004322:Drainage / Q000379:methods*; D005260:Female; D006801:Humans; D028421:Isoprostanes / Q000134:cerebrospinal fluid; D015227:Lipid Peroxidation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology
chemical_list: D028421:Isoprostanes