Reduction of brain lipid peroxidation by CSF drainage in Alzheimer's disease patients

Article type: Research Article

Authors: Praticò, Domenico^{a; *} | Yao, Yuemang^a | Rokach, Joshua^b | Mayo, Martha^c | Silverberg, Gerald G.^d | McGuire, Dawn^c

Affiliations: [a] Department of Pharmacology, The Center for Experimental Therapeutics, University of Pennsylvania, School of Medicine, Philadelphia, PA, 19104, USA | [b] Department of Chemistry, Florida Institute of Technology, Melbourne, FL, USA | [c] Eunoe, Inc., Redwood City, CA, 94063, USA and Department of Medicine and Neurology, UCSF Medical Center, San Francisco, CA, USA | [d] Department of Neurosurgery, Stanford University, School of Medicine, Stanford, CA, 94305, USA

Correspondence: [*] Corresponding author: Domenico Praticò, MD, Center for Experimental Therapeutics, University of Pennsylvania, BRB 2/3, room 812, 421, Curie Blvd, Philadelphia, PA 19104, USA. Tel.: +1 215 898 6446; Fax: +1 215 573 9004; E-mail: domenico@spirit.gcrc.upenn.edu.

Note: [] Communicated by M. Cristina Polidori

Abstract: Alzheimer's disease (AD) is associated with an increase in cerebrospinal fluid (CSF) levels of the isoprostane 8,12-iso-iPF2α-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-iPF2α-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.

Keywords: Alzheimer's disease, oxidative stress, isoprostanes, cerebrospinal fluid

DOI: 10.3233/JAD-2004-6405

Journal: Journal of Alzheimer's Disease, vol. 6, no. 4, pp. 385-389, 2004