Walton J R
Faculty of Medicine, University of New South Wales, St George Hospital, Sydney, Australia.
J Alzheimers Dis. 2014;40(4):765-838. doi: 10.3233/JAD-132204.
Industrialized societies produce many convenience foods with aluminum additives that enhance various food properties and use alum (aluminum sulfate or aluminum potassium sulfate) in water treatment to enable delivery of large volumes of drinking water to millions of urban consumers. The present causality analysis evaluates the extent to which the routine, life-long intake, and metabolism of aluminum compounds can account for Alzheimer's disease (AD), using Austin Bradford Hill's nine epidemiological and experimental causality criteria, including strength of the relationship, consistency, specificity, temporality, dose-dependent response, biological rationale, coherence with existing knowledge, experimental evidence, and analogy. Mechanisms that underlie the risk of low concentrations of aluminum relate to (1) aluminum's absorption rates, allowing the impression that aluminum is safe to ingest and as an additive in food and drinking water treatment, (2) aluminum's slow progressive uptake into the brain over a long prodromal phase, and (3) aluminum's similarity to iron, in terms of ionic size, allows aluminum to use iron-evolved mechanisms to enter the highly-active, iron-dependent cells responsible for memory processing. Aluminum particularly accumulates in these iron-dependent cells to toxic levels, dysregulating iron homeostasis and causing microtubule depletion, eventually producing changes that result in disconnection of neuronal afferents and efferents, loss of function and regional atrophy consistent with MRI findings in AD brains. AD is a human form of chronic aluminum neurotoxicity. The causality analysis demonstrates that chronic aluminum intake causes AD.
工业化社会生产出许多含有铝添加剂的方便食品，这些添加剂可增强食品的各种特性，并且在水处理中使用明矾（硫酸铝或硫酸铝钾），以便向数百万城市消费者供应大量饮用水。本因果关系分析采用奥斯汀·布拉德福德·希尔的九条流行病学和实验因果关系标准，包括关系强度、一致性、特异性、时间顺序、剂量反应关系、生物学合理性、与现有知识的连贯性、实验证据和类推法，评估铝化合物的日常、终身摄入和代谢在多大程度上可导致阿尔茨海默病（AD）。低浓度铝的风险背后的机制与以下方面有关：（1）铝的吸收率，这让人觉得摄入铝以及在食品和饮用水处理中添加铝是安全的；（2）铝在很长的前驱期缓慢渐进地进入大脑；（3）铝在离子大小方面与铁相似，这使得铝能够利用铁进化出的机制进入负责记忆处理的高活性、铁依赖性细胞。铝尤其会在这些铁依赖性细胞中蓄积至有毒水平，破坏铁稳态并导致微管耗竭，最终产生与AD大脑MRI结果一致的神经元传入和传出连接中断、功能丧失及局部萎缩的变化。AD是慢性铝神经毒性的一种人类形式。因果关系分析表明，长期摄入铝会导致AD。
