title: Oxidative signature of cerebrospinal fluid from mild cognitive impairment and Alzheimer disease patients.
abstract: BACKGROUND
  Several studies suggest that pathological changes in Alzheimer's disease (AD) brain begin around 10-20 years before the onset of cognitive impairment. Biomarkers that can support early diagnosis and predict development of dementia would, therefore, be crucial for patient care and evaluation of drug efficacy. Although cerebrospinal fluid (CSF) levels of Aβ42, tau, and p-tau are well-established diagnostic biomarkers of AD, there is an urgent need to identify additional molecular alterations of neuronal function that can be evaluated at the systemic level.
  
  
  OBJECTIVE
  This study was focused on the analysis of oxidative stress-related modifications of the CSF proteome, from subjects with AD and amnestic mild cognitive impairment (aMCI).
  
  
  METHODS
  A targeted proteomics approach has been employed to discover novel CSF biomarkers that can augment the diagnostic and prognostic accuracy of current leading CSF biomarkers. CSF samples from aMCI, AD and control individuals (CTR) were collected and analyzed using a combined redox proteomics approach to identify the specific oxidatively modified proteins in AD and aMCI compared with controls.
  
  
  RESULTS
  The majority of carbonylated proteins identified by redox proteomics are found early in the progression of AD, i.e., oxidatively modified CSF proteins were already present in aMCI compared with controls and remain oxidized in AD, thus suggesting that dysfunction of selected proteins initiate many years before severe dementia is diagnosed.
  
  
  CONCLUSIONS
  The above findings highlight the presence of early oxidative damage in aMCI before clinical dementia of AD is manifested. The identification of early markers of AD that may be detected peripherally may open new prospective for biomarker studies.
authors.affiliation: Department of Biochemical Sciences, Sapienza University of Rome, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Di Domenico
authors.affiliation: Department of Biochemical Sciences, Sapienza University of Rome, Italy.
authors.forename: Gilda
authors.initials: G
authors.lastname: Pupo
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Valencia, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Giraldo
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Valencia, Spain.
authors.forename: Mari-Carmen
authors.initials: MC
authors.lastname: Badìa
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Valencia, Spain.
authors.forename: Paloma
authors.initials: P
authors.lastname: Monllor
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Valencia, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Lloret
authors.affiliation: Department of Biochemical Sciences, Sapienza University of Rome, Italy.
authors.forename: Maria Eugenia
authors.initials: ME
authors.lastname: Schininà
authors.affiliation: Department of Biochemical Sciences, Sapienza University of Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Giorgi
authors.affiliation: Department of Biochemical Sciences, Sapienza University of Rome, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Cini
authors.affiliation: Department of Biochemical Sciences, Sapienza University of Rome, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Tramutola
authors.affiliation: Sanders-Brown Centre of Aging, Department of Chemistry, University of Kentucky, Lexington, KY, USA.
authors.forename: D Allan
authors.initials: DA
authors.lastname: Butterfield
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Valencia, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Viña
authors.affiliation: Department of Biochemical Sciences, Sapienza University of Rome, Italy. Electronic address: Marzia.perluigi@uniroma1.it.
authors.forename: Marzia
authors.initials: M
authors.lastname: Perluigi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D001057:Apolipoproteins E / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid; D016022:Case-Control Studies; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D020543:Proteome / Q000378:metabolism; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D015415:Biomarkers; D010446:Peptide Fragments; D020543:Proteome; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
keywords: APOE; Biomarkers; CSF; Extracellular chaperones; Protein oxidation; Redox proteomics