Altered Redox State in Whole Blood Cells from Patients with Mild Cognitive Impairment and Alzheimer’s Disease

Abstract

Oxidative stress plays an essential and early role in the pathophysiology of Alzheimer's disease (AD). Alterations in the redox state in AD and in mild cognitive impairment (MCI) patients appear in the brain and at peripheral level. Given that it is easier to study the latter, most of the research has been focused on plasma. However, the analysis of redox parameters in whole blood cells (including erythrocytes and leukocytes) has not really been investigated. Moreover, the association of these parameters with Mini-Mental State Examination (MMSE) clinical scores, has scarcely been studied. Therefore, the aim of the present work was to analyze several redox markers in whole blood cells from male and female MCI and AD patients. Antioxidant (superoxide dismutase, catalase (CAT), glutathione peroxidase (GPx), and reductase (GR) activities, and reduced glutathione (GSH) concentration) together with oxidant parameters (oxidized glutathione (GSSG) and thiobarbituric acid-reactive substances (TBARS)) were investigated using MCI and AD (10 women and 10 men in each group) and their age-matched control groups (15 women and 15 men). The results show an altered redox state in whole blood cells from AD patients (higher CAT, GSSG/GSH, TBARS and lower GPx, GR, GSH). Some of these redox parameters are already affected in MCI patients (higher TBARS and lower GPx and GR activities) in both sexes and, consequently, they could be used as markers of prodromal AD. Since GR, GSH, GSSG, and GSSG/GSH were found to be associated with MMSE scores, they seem to be useful clinically to monitor cognitive decline in AD progression.

Oxidative Stress in Patients with Advanced CKD and Renal Replacement Therapy: The Key Role of Peripheral Blood Leukocytes

“…Nevertheless, most research has been focused on the study of redox makers in serum or plasma, but not in immune cells. Since nutrition and diet significantly influence the extracellular redox status (plasma), and most enzymatic and non-enzymatic antioxidant mechanisms are intracellular [49], we analyzed the changes in several redox state parameters, not only in plasma but also in different types of peripheral leukocytes from advanced CKD patients. Furthermore, an optimal redox status of immune cells is essential for adequate homeostasis in the physiological systems [49].…”

Whole blood metabolomics of dementia patients reveal classes of disease-linked metabolites

“…may be important for maintaining CNS brain functions. Two compounds of Group C, SAM and GSSG, had been reported to be AD-and dementia-related markers (21,23). Group D contains 12 plasma compounds, half of which had been reported as AD-related markers.…”

“…Group C compounds were all enriched in RBCs, and four of six are novel dementia markers. Two of them (SAM, GSSG) were previously shown to be AD-related (21,23).…”

Altered central and blood glutathione in Alzheimer Disease and Mild Cognitive Impairment: a meta-analysis

“…Of the records screened, 40 studies were excluded as they were non-clinical studies (including reviews, editorials, and or conference abstracts), 70 studies were excluded because these studies involved non-human subjects, 81 studies were excluded as they were not conducted in AD or MCI patients, 23 studies were excluded as they were post-mortem studies, 9 studies were excluded as they did not include a healthy control group, 47 studies were excluded as they did not measure GSH in whole blood, plasma, or serum, and 2 were excluded as full results could not be obtained. A total of 27 studies quali ed, with 26 of these studies being included in the AD blood GSH meta-analysis(35-60), and 7 of these studies being included in the MCI analysis (38,39,41,42,45,51,61). Studies reporting GSH levels in different blood components (plasma, serum, blood cells) were analyzed as sub-studies, with a total of 31 studies/sub-studies used for AD blood GSH analysis and 8 studies/sub-studies used for MCI blood GSH analysis.…”