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Vol. 33, No. 4, 2012
Issue release date: July 2012
Free Access
Dement Geriatr Cogn Disord 2012;33:219–225
(DOI:10.1159/000338546)

Plasma Methionine Sulfoxide in Persons with Familial Alzheimer’s Disease Mutations

Ringman J.M.a · Fithian A.T.a · Gylys K.a,b · Cummings J.L.a,f · Coppola G.a · Elashoff D.a,c · Pratico D.g · Moskovitz J.h · Bitan G.a,d,e
aMary S. Easton Center for Alzheimer’s Disease Research, Department of Neurology, bSchool of Nursing, cDepartment of Medicine, dBrain Research Institute, and eMolecular Biology Institute, University of California at Los Angeles, Los Angeles, Calif; fCleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, Nev.; gTemple University School of Medicine, Philadelphia, Pa., and hDepartment of Pharmacology and Toxicology School of Pharmacy, University of Kansas, Lawrence, Kans., USA
email Corresponding Author

Abstract

Background: Convergent evidence suggests that oxidative stress plays a central role in the pathology of Alzheimer’s disease (AD). We asked if consequently, oxidation of methionine residues to methionine sulfoxide (MetO) was increased in plasma proteins of persons carrying familial AD (FAD) mutations. Methods: Plasma was collected from 31 persons from families harboring PSEN1 or APP mutations. Using Western blot analysis with a novel anti-MetO polyclonal antibody, MetO levels were measured and compared between FAD mutation carriers (MCs) and non-mutation carrying (NCs) kin. Results: A MetO-positive 120-kDa gel band distinguished FAD MCs and NCs (mean 11.4 ± 2.8 vs. 4.0 ± 3.1, p = 0.02). In a subset of subjects for whom both measurements were available, MetO levels correlated well with plasma F2-isoprostane (r = 0.81, p < 0.001) and superoxide dismutase 1 (r = 0.52, p = 0.004) levels. Conclusion: Our data provide evidence for elevated MetO levels in persons carrying FAD mutations that correlate with other indices of oxidative stress and suggest that plasma oxidative stress markers may be useful for diagnosis of AD.


 Outline


 goto top of outline Key Words

  • Oxidative stress
  • Isoprostanes
  • Plasma
  • Superoxide dismutase
  • Presenilin-1
  • Amyloid β-protein precursor

 goto top of outline Abstract

Background: Convergent evidence suggests that oxidative stress plays a central role in the pathology of Alzheimer’s disease (AD). We asked if consequently, oxidation of methionine residues to methionine sulfoxide (MetO) was increased in plasma proteins of persons carrying familial AD (FAD) mutations. Methods: Plasma was collected from 31 persons from families harboring PSEN1 or APP mutations. Using Western blot analysis with a novel anti-MetO polyclonal antibody, MetO levels were measured and compared between FAD mutation carriers (MCs) and non-mutation carrying (NCs) kin. Results: A MetO-positive 120-kDa gel band distinguished FAD MCs and NCs (mean 11.4 ± 2.8 vs. 4.0 ± 3.1, p = 0.02). In a subset of subjects for whom both measurements were available, MetO levels correlated well with plasma F2-isoprostane (r = 0.81, p < 0.001) and superoxide dismutase 1 (r = 0.52, p = 0.004) levels. Conclusion: Our data provide evidence for elevated MetO levels in persons carrying FAD mutations that correlate with other indices of oxidative stress and suggest that plasma oxidative stress markers may be useful for diagnosis of AD.

Copyright © 2012 S. Karger AG, Basel


 goto top of outline Author Contacts

Gal Bitan, PhD
David Geffen School of Medicine, University of California at Los Angeles
Neuroscience Research Building 1, Room 451
635 Charles E. Young Drive South, Los Angeles, CA 90095–7334 (USA)
Tel. +1 310 206 2082, E-Mail gbitan@mednet.ucla.edu


 goto top of outline Article Information

Accepted: March 30, 2012
Published online: May 14, 2012
Number of Print Pages : 7


 goto top of outline Publication Details

Dementia and Geriatric Cognitive Disorders

Vol. 33, No. 4, Year 2012 (Cover Date: July 2012)

Journal Editor: Chan-Palay V. (Boston, Mass.)
ISSN: 1420-8008 (Print), eISSN: 1421-9824 (Online)

For additional information: http://www.karger.com/DEM


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

Background: Convergent evidence suggests that oxidative stress plays a central role in the pathology of Alzheimer’s disease (AD). We asked if consequently, oxidation of methionine residues to methionine sulfoxide (MetO) was increased in plasma proteins of persons carrying familial AD (FAD) mutations. Methods: Plasma was collected from 31 persons from families harboring PSEN1 or APP mutations. Using Western blot analysis with a novel anti-MetO polyclonal antibody, MetO levels were measured and compared between FAD mutation carriers (MCs) and non-mutation carrying (NCs) kin. Results: A MetO-positive 120-kDa gel band distinguished FAD MCs and NCs (mean 11.4 ± 2.8 vs. 4.0 ± 3.1, p = 0.02). In a subset of subjects for whom both measurements were available, MetO levels correlated well with plasma F2-isoprostane (r = 0.81, p < 0.001) and superoxide dismutase 1 (r = 0.52, p = 0.004) levels. Conclusion: Our data provide evidence for elevated MetO levels in persons carrying FAD mutations that correlate with other indices of oxidative stress and suggest that plasma oxidative stress markers may be useful for diagnosis of AD.



 goto top of outline Author Contacts

Gal Bitan, PhD
David Geffen School of Medicine, University of California at Los Angeles
Neuroscience Research Building 1, Room 451
635 Charles E. Young Drive South, Los Angeles, CA 90095–7334 (USA)
Tel. +1 310 206 2082, E-Mail gbitan@mednet.ucla.edu


 goto top of outline Article Information

Accepted: March 30, 2012
Published online: May 14, 2012
Number of Print Pages : 7


 goto top of outline Publication Details

Dementia and Geriatric Cognitive Disorders

Vol. 33, No. 4, Year 2012 (Cover Date: July 2012)

Journal Editor: Chan-Palay V. (Boston, Mass.)
ISSN: 1420-8008 (Print), eISSN: 1421-9824 (Online)

For additional information: http://www.karger.com/DEM


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.