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职业性铝暴露及其与认知功能的淀粉样变关联。

Occupational exposure to aluminum and its amyloidogenic link with cognitive functions.

作者信息

Zawilla N H, Taha F M, Kishk N A, Farahat S A, Farghaly M, Hussein M

机构信息

Department of Occupational & Environmental Medicine, Faculty of Medicine, Cairo University, Egypt.

Department of Medical Biochemistry, Faculty of Medicine, Cairo University, Egypt.

出版信息

J Inorg Biochem. 2014 Oct;139:57-64. doi: 10.1016/j.jinorgbio.2014.06.003. Epub 2014 Jun 11.

DOI:10.1016/j.jinorgbio.2014.06.003
PMID:24973993
Abstract

As many other metals, aluminum is a widely recognized neurotoxicant and its link with neurodegenerative disorders has been the subject of scientific debate. One proposal focuses on amyloid β deposition (amyloidogenesis) as the key player in triggering neuronal dysfunction the so-called amyloid cascade hypothesis. We undertook this study first to investigate the cognition status of workers exposed to Al dust in an Al factory in Southern Cairo, second, to evaluate serum amyloid precursor protein (APP) and cathepsin D (CD) enzyme activity to study the possible role of Al in amyloidogenesis, and finally to explore the relation between these potential biomarkers and cognitive functions. The study was conducted on 54 exposed workers and 51 matched controls. They were subjected to questionnaire, neurological examination and a cognitive test battery, Addenbrooke's Cognitive Examination - Revised (ACE-R). Serum Al, APP and CD enzyme activity were measured. A significant increase of serum Al was found in the exposed workers with an associated increase in serum APP and decrement in CD activity. The exposed workers displayed poor performance on the ACE-R test. No significant correlation was detected between ACE-R test total score and either APP or CD activity. We concluded that occupational exposure to Al is associated with cognitive impairment. The effect of occupational Al exposure on the serum levels of APP and CD activity may be regarded as a possible mechanism of Al in amyloidogenesis. However, our findings do not support the utility of serum APP and CD activity as screening markers for early or preclinical cognitive impairment.

摘要

与许多其他金属一样,铝是一种广为人知的神经毒素,其与神经退行性疾病的关联一直是科学争论的焦点。一种观点认为淀粉样β蛋白沉积(淀粉样蛋白生成)是引发神经元功能障碍的关键因素,即所谓的淀粉样蛋白级联假说。我们开展这项研究,一是为了调查开罗南部一家铝厂接触铝粉尘工人的认知状况,二是评估血清淀粉样前体蛋白(APP)和组织蛋白酶D(CD)的酶活性,以研究铝在淀粉样蛋白生成中可能发挥的作用,最后探究这些潜在生物标志物与认知功能之间的关系。该研究对54名接触铝粉尘的工人和51名匹配的对照组人员进行。他们接受了问卷调查、神经学检查以及一套认知测试,即修订版的Addenbrooke认知检查(ACE-R)。测定了血清铝、APP和CD的酶活性。结果发现,接触铝粉尘的工人血清铝显著升高,同时血清APP升高,CD活性降低。接触铝粉尘的工人在ACE-R测试中的表现较差。未检测到ACE-R测试总分与APP或CD活性之间存在显著相关性。我们得出结论,职业性接触铝与认知障碍有关。职业性接触铝对血清APP水平和CD活性的影响可能被视为铝在淀粉样蛋白生成中的一种可能机制。然而,我们的研究结果并不支持将血清APP和CD活性用作早期或临床前认知障碍的筛查标志物。

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