Increased iron and free radical generation in preclinical Alzheimer disease and mild cognitive impairment.
Increased iron and free radical generation in preclinical Alzheimer disease and mild cognitive impairment.
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DOI：
10.3233/jad-2010-1239
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Perry G
中科院分区：
文献类型：
--
作者：
Smith MA;Zhu X;Tabaton M;Liu G;McKeel DW Jr;Cohen ML;Wang X;Siedlak SL;Dwyer BE;Hayashi T;Nakamura M;Nunomura A;Perry G
现在已经确定，氧化应激是阿尔茨海默病（AD）发病机制中最早发生的变化之一。与此一致，轻度认知障碍（MCI），AD的临床前体，也以氧化应激升高为特征。由于这种压力不会在真空中起作用，在这项研究中，我们试图确定是否氧化还原活性铁，一种有效的自由基来源，在MCI和临床前AD相比，认知功能完整的年龄匹配的对照患者升高。在临床前AD/MCI病例中，皮质和小脑中的铁水平最高。有趣的是，在临床前AD患者中，小脑中氧化还原活性铁的神经胶质积累也很明显，并且随着患者逐渐认知受损而增加。我们的研究结果表明，铁稳态失衡是导致AD的神经退行性过程的前兆，并且铁失衡不一定是受影响区域所独有的。事实上，了解大脑其他区域的铁沉积可能会为神经保护策略提供见解。在AD的临床前阶段的铁沉积可能是有用的诊断工具，使用铁成像方法，以及潜在的治疗靶点，通过金属离子螯合剂。
It is now established that oxidative stress is one of the earliest, if not the earliest, change that occurs in the pathogenesis of Alzheimer's disease (AD). Consistent with this, mild cognitive impairment (MCI), the clinical precursor of AD, is also characterized by elevations in oxidative stress. Since such stress does not operate in vacuo, in this study we sought to determine whether redox-active iron, a potent source of free radicals, was elevated in MCI and preclinical AD as compared to cognitively-intact age-matched control patients. Increased iron was found at the highest levels both in the cortex and cerebellum from the pre-clinical AD/MCI cases. Interestingly, glial accumulations of redox-active iron in the cerebellum were also evident in preclinical AD patients and tend to increase as patients became progressively cognitively impaired. Our findings suggests that an imbalance in iron homeostasis is a precursor to the neurodegenerative processes leading to AD and that iron imbalance is not necessarily unique to affected regions. In fact, an understanding of iron deposition in other regions of the brain may provide insights into neuroprotective strategies. Iron deposition at the preclinical stage of AD may be useful as a diagnostic tool, using iron imaging methods, as well as a potential therapeutic target, through metal ion chelators.