TY - JOUR
T1 - Oxidative signature of cerebrospinal fluid from mild cognitive impairment and Alzheimer disease patients
AU - Di Domenico, Fabio
AU - Pupo, Gilda
AU - Giraldo, Esther
AU - Badìa, Mari Carmen
AU - Monllor, Paloma
AU - Lloret, Ana
AU - Eugenia Schininà, Maria
AU - Giorgi, Alessandra
AU - Cini, Chiara
AU - Tramutola, Antonella
AU - Butterfield, D. Allan
AU - Viña, José
AU - Perluigi, Marzia
N1 - Publisher Copyright:
© 2015 Published by Elsevier Inc.
PY - 2016/2/1
Y1 - 2016/2/1
N2 - 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. Objectives 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.
AB - 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. Objectives 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.
KW - APOE
KW - Biomarkers
KW - CSF
KW - Extracellular chaperones
KW - Protein oxidation
KW - Redox proteomics
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U2 - 10.1016/j.freeradbiomed.2015.12.004
DO - 10.1016/j.freeradbiomed.2015.12.004
M3 - Article
C2 - 26675344
AN - SCOPUS:84949509857
SN - 0891-5849
VL - 91
SP - 1
EP - 9
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
ER -