Oxidative signature of cerebrospinal fluid from mild cognitive impairment and Alzheimer disease patients

Domenico, Fabio Di; Pupo, Gilda; Giraldo, Esther; Badia, Mari Carmen; Monllor, Paloma; Lloret, Ana; Schininà, Maria Eugenia; Giorgi, Alessandra; Cini, Chiara; Tramutola, Antonella; Butterfield, D. Allan; Viña, José; Perluigi, Marzia

doi:10.1016/j.freeradbiomed.2015.12.004

Cited by 79 publications

(39 citation statements)

References 50 publications

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“…Different studies regarding protein oxidation in AD patients have been conducted over the past several years. Most of these studies found that in CSF, there is an increase in protein modifications by oxidation, such as in coenzyme Q-10 [ 6, 7 ]. By contrast, in other studies the protein studied, such as transthyretin, is less oxidized in AD patients [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Increased Albumin Oxidation in Cerebrospinal Fluid and Plasma from Alzheimer’s Disease Patients

Costa

Horrillo

Ortiz

et al. 2018

JAD

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Background:Oxidative stress in the brain and peripheral systems is considered a major player in Alzheimer’s disease (AD). Albumin is the main transporter and the main extracellular antioxidant in the human body.Objective:Here we explore for the first time the oxidation status of cerebrospinal fluid (CSF) and plasma albumin in AD in comparison to healthy subjects.Methods:Plasma and CSF samples were obtained from mild-moderate AD patients and control healthy age-matched donors. Albumin redox state forms (reduced: HMA; reversibly oxidized: HNA1; irreversibly oxidized: HNA2) were determined by HPLC. Albumin post-translational modifications (PTM) analysis was performed by mass spectrometry.Results:HPLC showed less HMA in AD plasma than in controls (54.1% versus 65.2% ; p < 0.0001), mainly at expense of HNA1 (42.8% versus 32.5% ; p < 0.0001). In AD CSF, HMA was drastically decreased compared to controls (9.6% versus 77.4% ; p < 0.0001), while HNA2 was increased (52.8% versus 7.4% ; p < 0.0001). In AD patients but not in healthy controls, CSF albumin was much more irreversibly oxidized than in plasma (close to 20-fold increase in HNA2). PTM analysis showed that AD CSF albumin samples behave as a differentiated cluster, thus confirming the albumin oxidative pattern observed by HPLC.Conclusion:CSF albumin oxidation in AD patients was dramatically increased comparing to healthy controls, while in plasma this increase was smaller. CSF albumin in AD patients was much more oxidized than in plasma, but this effect was not observed in healthy controls. These results suggest that albumin oxidation, especially in CSF, and its role in AD deserves further investigation.

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Section: Discussionmentioning

confidence: 99%

Increased Albumin Oxidation in Cerebrospinal Fluid and Plasma from Alzheimer’s Disease Patients

Costa

Horrillo

Ortiz

et al. 2018

JAD

View full text Add to dashboard Cite

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“…Of note, apoE structure could play a role since apoE2 has two Cys residues, whereas apoE3 has only one Cys and apoE4 has no free thiol group; therefore, the lower number of Cys residues in apo E4 would lead to a lesser protection against oxidative stress. Oxidation of apoE, evidenced by analysis of oxidative stress-related modifications of the cerebrospinal fluid (CSF) proteome, could thus affect thiol-mediated antioxidant activity, which would allow excess oxidative damage to the lipoprotein particles and promote Aβ protein aggregation [110] .…”

Section: Linking Oxidative Stress and Admentioning

confidence: 99%

Oxidative stress and the amyloid beta peptide in Alzheimer’s disease

et al. 2018

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Oxidative stress is known to play an important role in the pathogenesis of a number of diseases. In particular, it is linked to the etiology of Alzheimer’s disease (AD), an age-related neurodegenerative disease and the most common cause of dementia in the elderly. Histopathological hallmarks of AD are intracellular neurofibrillary tangles and extracellular formation of senile plaques composed of the amyloid-beta peptide (Aβ) in aggregated form along with metal-ions such as copper, iron or zinc. Redox active metal ions, as for example copper, can catalyze the production of Reactive Oxygen Species (ROS) when bound to the amyloid-β (Aβ). The ROS thus produced, in particular the hydroxyl radical which is the most reactive one, may contribute to oxidative damage on both the Aβ peptide itself and on surrounding molecule (proteins, lipids, …). This review highlights the existing link between oxidative stress and AD, and the consequences towards the Aβ peptide and surrounding molecules in terms of oxidative damage. In addition, the implication of metal ions in AD, their interaction with the Aβ peptide and redox properties leading to ROS production are discussed, along with both in vitro and in vivo oxidation of the Aβ peptide, at the molecular level.

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“…With respect to inflammatory pathways, the proinflammatory chitinase YKL-40, which was isolated initially in a proteomic screen, displayed significantly higher levels in CDR 0.5 and 1 compared with CDR 0 individuals in a discovery and validation cohort, with CSF YKL-40/Aβ 42 ratio predicting the conversion from CDR 0 to CDR > 0, as well as total tau/Aβ42 and phospho-tau (T181)/Aβ 42 [85]. Other notable promising CSF candidate markers include protein modulators of the endosomal-autophagy-lysosomal system [86], which may reflect the major disturbances found in these pathways in MCI and AD [87][88][89]; protein and lipid markers of oxidative stress in MCI and AD [90][91][92]; and alterations in microRNA profiles that may reflect underlying dysregulation of amyloid and tau pathways [93][94][95]. Two recent metareviews [96,97] provide a current state of the field with respect to the utility of CSF core ( Fig.…”

Section: Novel Csf Biomarkersmentioning

confidence: 99%

Biomarkers for the Early Detection and Progression of Alzheimer's Disease

et al. 2017

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The recent failures of potential disease-modifying drugs for Alzheimer's disease (AD) may reflect the fact that the enrolled participants in clinical trials are already too advanced to derive a clinical benefit. Thus, well-validated biomarkers for the early detection and accurate diagnosis of the preclinical stages of AD will be crucial for therapeutic advancement. The combinatorial use of biomarkers derived from biological fluids, such as cerebrospinal fluid (CSF), with advanced molecular imaging and neuropsychological testing may eventually achieve the diagnostic sensitivity and specificity necessary to identify people in the earliest stages of the disease when drug modification is most likely possible. In this regard, positive amyloid or tau tracer retention on positron emission tomography imaging, low CSF concentrations of the amyloid-β 1-42 peptide, high CSF concentrations in total tau and phospho-tau, mesial temporal lobe atrophy on magnetic resonance imaging, and temporoparietal/precuneus hypometabolism or hypoperfusion on 18F-fluorodeoxyglucose positron emission tomography have all emerged as biomarkers for the progression to AD. However, the ultimate AD biomarker panel will likely involve the inclusion of novel CSF and blood biomarkers more precisely associated with confirmed pathophysiologic mechanisms to improve its reliability for detecting preclinical AD. This review highlights advancements in biological fluid and imaging biomarkers that are moving the field towards achieving the goal of a preclinical detection of AD.

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Oxidative signature of cerebrospinal fluid from mild cognitive impairment and Alzheimer disease patients

Cited by 79 publications

References 50 publications

Increased Albumin Oxidation in Cerebrospinal Fluid and Plasma from Alzheimer’s Disease Patients

Increased Albumin Oxidation in Cerebrospinal Fluid and Plasma from Alzheimer’s Disease Patients

Oxidative stress and the amyloid beta peptide in Alzheimer’s disease

Biomarkers for the Early Detection and Progression of Alzheimer's Disease

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