Department of Genetics, Physiology and Microbiology (Unit of Animal Physiology), Faculty of Biology, Complutense University, Madrid, Spain.
Institute of Biomedical Research Hospital 12 Octubre (imas12), Madrid, Spain.
J Alzheimers Dis. 2019;71(1):153-163. doi: 10.3233/JAD-190198.
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.
氧化应激在阿尔茨海默病 (AD) 的病理生理学中起着至关重要和早期的作用。AD 和轻度认知障碍 (MCI) 患者的氧化还原状态改变出现在大脑和外周水平。由于研究后者更容易,因此大多数研究都集中在血浆上。然而,尚未真正研究全血细胞(包括红细胞和白细胞)中的氧化还原参数。此外,这些参数与 Mini-Mental State Examination (MMSE) 临床评分的相关性也很少被研究。因此,本工作的目的是分析 MCI 和 AD 男性和女性患者全血中的几种氧化还原标志物。抗氧化剂(超氧化物歧化酶、过氧化氢酶 (CAT)、谷胱甘肽过氧化物酶 (GPx) 和还原酶 (GR) 活性以及还原型谷胱甘肽 (GSH) 浓度)以及氧化剂参数(氧化型谷胱甘肽 (GSSG) 和硫代巴比妥酸反应物质 (TBARS)) 使用 MCI 和 AD(每组 10 名女性和 10 名男性)及其年龄匹配的对照组(每组 15 名女性和 15 名男性)进行了研究。结果表明,AD 患者全血的氧化还原状态发生改变(CAT、GSSG/GSH、TBARS 升高,GPx、GR、GSH 降低)。这些氧化还原参数中的一些已经在 MCI 患者中受到影响(TBARS 升高和 GPx 和 GR 活性降低),且在两性中均如此,因此它们可能作为 AD 前驱期的标志物。由于 GR、GSH、GSSG 和 GSSG/GSH 与 MMSE 评分相关,因此它们似乎在临床上有助于监测 AD 进展中的认知能力下降。