Sultana Rukhsana, Baglioni Mauro, Cecchetti Roberta, Cai Jian, Klein Jon B, Bastiani Patrizia, Ruggiero Carmelinda, Mecocci Patrizia, Butterfield D Allan
Department of Chemistry, Center of Membrane Sciences, Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40506-0055, USA.
Institute of Gerontology and Geriatrics, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy.
Free Radic Biol Med. 2013 Dec;65:595-606. doi: 10.1016/j.freeradbiomed.2013.08.001. Epub 2013 Aug 8.
Alzheimer disease (AD) is an age-related neurodegenerative condition. AD is histopathologically characterized by the presence of three main hallmarks: senile plaques (rich in amyloid-β peptide), neuronal fibrillary tangles (rich in phosphorylated tau protein), and synapse loss. However, definitive biomarkers for this devastating disease in living people are still lacking. In this study, we show that levels of oxidative stress markers are significantly increased in the mitochondria isolated from lymphocytes of subjects with mild cognitive impairment (MCI) compared to cognitively normal individuals. Further, an increase in mitochondrial oxidative stress in MCI is associated with MMSE score, vitamin E components, and β-carotene. Further, a proteomics approach showed that alterations in the levels of thioredoxin-dependent peroxide reductase, myosin light polypeptide 6, and ATP synthase subunit β might be important in the progression and pathogenesis of AD. Increased understanding of oxidative stress and protein alterations in easily obtainable peripheral tissues will be helpful in developing biomarkers to combat this devastating disorder.
阿尔茨海默病（AD）是一种与年龄相关的神经退行性疾病。AD在组织病理学上的特征是存在三个主要标志：老年斑（富含β-淀粉样肽）、神经元纤维缠结（富含磷酸化tau蛋白）和突触丧失。然而，对于这种在活人身上具有毁灭性的疾病，仍然缺乏确切的生物标志物。在本研究中，我们发现与认知正常个体相比，轻度认知障碍（MCI）受试者淋巴细胞分离出的线粒体中氧化应激标志物水平显著升高。此外，MCI中线粒体氧化应激的增加与简易精神状态检查表（MMSE）评分、维生素E成分和β-胡萝卜素有关。此外，蛋白质组学方法表明，硫氧还蛋白依赖性过氧化物还原酶、肌球蛋白轻链多肽6和ATP合酶β亚基水平的改变可能在AD的进展和发病机制中起重要作用。增加对易于获取的外周组织中氧化应激和蛋白质改变的了解将有助于开发对抗这种毁灭性疾病的生物标志物。
