In the brain, Oxidative Stress (OS) contribute to structural and functional changes associated with vascular aging, such as endothelial dysfunction, extracellular matrix degradation, resulting in age-related reduced vasodilatation in response to agonists. For this reason, OS is considered a key factor in Alzheimer’s Disease (AD) development and recent evidence correlated oxidative stress with vascular lesion in the pathogenesis of AD, but the mechanism still need to be fully clarified. The etiology of AD is still not completely understood and is influenced by several factors including Apolipoprotein E (ApoE) genotype. In particular, the Apo ε4 isoform is considered a risk factor for AD development. This study was aimed to evaluate the possible relationship between three plasmatic OS marker and Apo ε4 carrier status. Plasmatic soluble receptor for advanced glycation end products (sRAGE) levels, plasma antioxidant total defenses (by lag-time method) and plasmatic Reactive Oxygen species (ROS) levels were evaluated in 25 AD patients and in 30 matched controls. ROS were significantly higher while plasma antioxidant total defenses and sRAGE levels were significantly lower in AD patients compared to controls. In AD patients lag-time values show a significant positive linear correlation with sRAGE levels and a (even not significant) negative correlation with ROS levels. Lag-time is significantly lower in ε4 carrier (N = 13) than in ε4 non-carrier (N = 12). Our result confirms the substantial OS in AD. Lag-time levels showed a significant positive correlation with sRAGE levels and a significant association with ε4 carrier status suggesting that plasmatic lag-time evaluation can be considered as a potential useful OS risk marker in AD.

中文翻译：

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阿尔茨海默氏病患者的滞后时间：与ApoE4亚型相关的潜在血浆氧化应激指标

在大脑中，氧化应激（OS）会导致与血管衰老相关的结构和功能变化，例如内皮功能障碍，细胞外基质降解，从而导致与年龄相关的激动剂引起的血管舒张减少。因此，OS被认为是阿尔茨海默氏病（AD）发展的关键因素，最近的证据表明氧化应激与AD发病机理中的血管病变有关，但其机理仍需充分阐明。AD的病因仍未完全了解，并受包括载脂蛋白E（ApoE）基因型在内的几个因素的影响。特别是，Apoε4同工型被认为是AD发育的危险因素。本研究旨在评估三种血浆OS标记物与Apoε4携带者状态之间的可能关系。在25位AD患者和30位相匹配的对照组中评估了晚期糖基化终末产物（sRAGE）水平，血浆抗氧化剂的总防御能力（​​通过滞后时间方法）和血浆活性氧水平（ROS）的血浆可溶性受体。与对照组相比，AD患者的ROS显着升高，而血浆抗氧化剂的总防御和sRAGE水平则显着降低。在AD患者中，滞后时间值与sRAGE水平呈显着正线性相关，与ROS水平呈负相关（甚至不显着）。滞后时间在ε4载波（N = 13）中比在ε4非载波（N = 12）中要低得多。我们的结果证实了AD中的大量操作系统。