title: Plasma methionine sulfoxide in persons with familial Alzheimer's disease mutations.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Mary S. Easton Center for Alzheimer's Disease Research, Department of Neurology, University of California at Los Angeles, Los Angeles, CA 90095-7334, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Ringman
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Fithian
authors.forename: Karen
authors.initials: K
authors.lastname: Gylys
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Cummings
authors.forename: Giovanni
authors.initials: G
authors.lastname: Coppola
authors.forename: David
authors.initials: D
authors.lastname: Elashoff
authors.forename: Domenico
authors.initials: D
authors.lastname: Pratico
authors.forename: Jackob
authors.initials: J
authors.lastname: Moskovitz
authors.forename: Gal
authors.initials: G
authors.lastname: Bitan
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000097:blood* / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000704:Analysis of Variance; D001057:Apolipoproteins E / Q000235:genetics; D001798:Blood Proteins / Q000235:genetics; D015153:Blotting, Western; D004247:DNA / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D028421:Isoprostanes / Q000097:blood; D008297:Male; D008715:Methionine / Q000031:analogs & derivatives* / Q000097:blood; D009154:Mutation / Q000235:genetics / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D053764:Presenilin-1 / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1
chemical_list: D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; D001798:Blood Proteins; D028421:Isoprostanes; C508853:PSEN1 protein, human; D053764:Presenilin-1; C000606290:SOD1 protein, human; D004247:DNA; D008715:Methionine; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; C013111:methionine sulfoxide