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Article type: Research Article
Authors: Martínez de Toda, Irenea; b | Miguélez, Laraa | Vida, Carmena; b | Carro, Evab; c | De la Fuente, Mónicaa; b; *
Affiliations: [a] Department of Genetics, Physiology and Microbiology (Unit of Animal Physiology), Faculty of Biology, Complutense University, Madrid, Spain | [b] Institute of Biomedical Research Hospital 12 Octubre (imas12), Madrid, Spain | [c] Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
Correspondence: [*] Correspondence to: Mónica De la Fuente, PhD, MD, Department of Genetics, Physiology and Microbiology (Unit of Animal Physiology), Faculty of Biology, Complutense University, José Antonio Nováis 12, 28040 Madrid, Spain. Tel.: +34 91 394 4989; E-mail: mondelaf@bio.ucm.es.
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.
Keywords: Antioxidants, cognitive dysfunction, neurodegenerative diseases, oxidants, oxidative stress, preclinical markers
DOI: 10.3233/JAD-190198
Journal: Journal of Alzheimer's Disease, vol. 71, no. 1, pp. 153-163, 2019
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