Don Carlo Gnocchi Foundation, Santa Maria Nascente Clinical Research Center, Milan, Italy. mgironi @ dongnocchi.it
Neurodegener Dis. 2011;8(3):129-37. doi: 10.1159/000319452. Epub 2010 Sep 13.
Byproducts of oxidative metabolic reactions could play a role in the pathogenesis of several neurodegenerative diseases (ND) including Alzheimer's disease (AD). We designed a study aimed at investigating a large set of oxidative and antioxidant markers in a sample of patients affected by different forms of dementia or memory impairment.
Serum levels of coenzyme Q(10), malondialdehyde (MDA), the total, oxidized and reduced forms of glutathione (GStot, GSSG and GSH, respectively), reactive oxygen species, anti-oxidized low-density lipoprotein antibodies and antioxidant power (PAO) were investigated in patients affected by AD, mild cognitive impairment, dementia with Lewy bodies and Parkinson's disease with dementia. The patient sample (n = 66) was compared with healthy subjects (HC; n = 62), and a comparison across pathological subgroups was also performed. A multivariate logistic regression model was implemented in order to calculate an algorithm model for predicting the risk of developing a neurodegenerative disorder.
The comparison between the memory deficit (MD) group and HC showed a significant difference for MDA (MD: 6.3 ± 2.8 μg/l; HC: 9.1 ± 4.9 μg/l; p = 1.7 × 10(-6)), GStot (MD: 260.4 ± 62.6 mg/l; HC: 306.5 ± 60.7 mg/l; p = 2.2 × 10(-5)), GSH (MD: 208.9 ± 68.4 mg/l; HC: 295.3 ± 101.3 mg/l; p = 2.2 × 10(-7)) and PAO (MD: 1,066.5 ± 247.7 μmol; HC: 954.9 ± 200.4 μmol; p = 0.8 × 10(-3)). By contrast, no differences in the levels of the studied markers were detected across the different forms of ND. An older age, higher levels of PAO, lower levels of GSH and MDA and the use of cardiovascular or antidepressant drugs were the most important factors associated with the carrier ship of neurodegenerative disorder.
To our knowledge, this is the first study reporting similar oxidative imbalance in different forms of memory impairment, regardless of the specific etiology. Low GSH levels could be considered as a favorable factor in ND; at the same time it could be suggested that higher levels of PAO represent a counteracting mechanism against an increased oxidative stress. The association between vascular risk factors, depressive status and cognitive impairment is in line with findings in the literature.
氧化代谢反应的副产物可能在几种神经退行性疾病（ND）的发病机制中发挥作用，包括阿尔茨海默病（AD）。我们设计了一项研究，旨在调查一组不同形式的痴呆或记忆障碍患者的大量氧化和抗氧化标志物。
我们检测了 AD、轻度认知障碍、路易体痴呆和帕金森病伴痴呆患者的辅酶 Q(10)、丙二醛（MDA）、总谷胱甘肽（GStot）、氧化谷胱甘肽（GSSG）和还原谷胱甘肽（GSH）、活性氧、抗氧化低密度脂蛋白抗体和抗氧化能力（PAO）的血清水平。患者样本（n=66）与健康对照组（HC；n=62）进行比较，还对不同病理亚组进行了比较。实施了多变量逻辑回归模型，以计算预测神经退行性疾病发展风险的算法模型。
记忆障碍（MD）组与 HC 之间的比较显示 MDA（MD：6.3±2.8 μg/l；HC：9.1±4.9 μg/l；p=1.7×10(-6))、GStot（MD：260.4±62.6 mg/l；HC：306.5±60.7 mg/l；p=2.2×10(-5))、GSH（MD：208.9±68.4 mg/l；HC：295.3±101.3 mg/l；p=2.2×10(-7))和 PAO（MD：1066.5±247.7 μmol；HC：954.9±200.4 μmol；p=0.8×10(-3))存在显著差异。相比之下，不同形式的 ND 之间没有检测到研究标志物水平的差异。年龄较大、PAO 水平较高、GSH 和 MDA 水平较低以及使用心血管或抗抑郁药物是与携带神经退行性疾病相关的最重要因素。
据我们所知，这是第一项报告不同形式的记忆障碍存在相似氧化失衡的研究，无论其具体病因如何。较低的 GSH 水平可能被认为是 ND 的有利因素；同时，较高的 PAO 水平可能代表了一种对抗氧化应激增加的拮抗机制。血管危险因素、抑郁状态和认知障碍之间的关联与文献中的发现一致。
