title: d-penicillamine reduces serum oxidative stress in Alzheimer's disease patients.
abstract: BACKGROUND
  Several lines of evidence address the emerging role for copper in Alzheimer's disease (AD) for sustaining oxidative mechanisms. Studies indicate that peripheral markers of oxidative stress in AD patients could be informative about the pathophysiology of this brain condition. Here, we present a pilot study examining the efficacy of the copper-chelating agent d-penicillamine in reducing oxidative stress in AD patients.
  
  
  METHODS
  Serum levels of copper sampled in AD patients and healthy controls indicate a copper homeostasis imbalance in AD. On this basis, 34 AD patients were enrolled in a 6-month, double-blind, placebo-controlled trial with the copper d-penicillamine-chelating agent. Nine patients for each group completed the trial. Oxidative stress, trace metals and clinical parameters were evaluated.
  
  
  RESULTS
  At the start of the study (t0) total peroxides and copper serum content of AD patients were higher (P < 0.0001, P < 0.0001, respectively) and antioxidants were lower (P < 0.05) than in healthy controls. Copper and peroxides were correlated in the AD population (Pearson's r = 0.61, P < 0.001). After treatment with d-penicillamine, the extent of oxidative stress (P < 0.05) was decreased, but no difference was observed in the rate of cognitive decline.
  
  
  CONCLUSIONS
  Data from this pilot study suggest that copper could play a role in the production of peroxides in AD, and that d-penicillamine has an effect in reducing oxidative damage, however, results are still inconclusive in terms of drug efficacy on the clinical progression of AD. Studies with larger cohorts are needed to elucidate the real effectiveness of d-penicillamine treatment in AD.
authors.affiliation: AFaR, Ospedale Fatebenefratelli, Rome, Italy. squitti@iess.rm.cnr.it
authors.forename: R
authors.initials: R
authors.lastname: Squitti
authors.forename: P M
authors.initials: PM
authors.lastname: Rossini
authors.forename: E
authors.initials: E
authors.lastname: Cassetta
authors.forename: F
authors.initials: F
authors.lastname: Moffa
authors.forename: P
authors.initials: P
authors.lastname: Pasqualetti
authors.forename: M
authors.initials: M
authors.lastname: Cortesi
authors.forename: A
authors.initials: A
authors.lastname: Colloca
authors.forename: L
authors.initials: L
authors.lastname: Rossi
authors.forename: A
authors.initials: A
authors.lastname: Finazzi-Agró
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism*; D002614:Chelating Agents / Q000008:administration & dosage*; D003300:Copper / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D006801:Humans; D007501:Iron / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D010396:Penicillamine / Q000008:administration & dosage*; D010865:Pilot Projects; D012189:Retrospective Studies
chemical_list: D002614:Chelating Agents; D003300:Copper; D007501:Iron; D010396:Penicillamine