Aluminum induces tau aggregation in vitro but not in vivo.
Aluminum induces tau aggregation in vitro but not in vivo.
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DOI：
10.3233/jad-2007-11401
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发表时间：
2007
期刊：
影响因子：
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通讯作者：
T. Mizoroki;S. Meshitsuka;S. Maeda;M. Murayama;N. Sahara;A. Takashima
中科院分区：
文献类型：
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作者：
T. Mizoroki;S. Meshitsuka;S. Maeda;M. Murayama;N. Sahara;A. Takashima
病因学研究表明，摄入铝（Al）可能会增加个体患阿尔茨海默病（AD）的风险。然而，关于Al效应的生化分析数据并不一致。因此，Al在AD中的病理参与尚不清楚。如果阿尔茨海默病与Al有关，那么我们可以合理地假设Al可能参与淀粉样斑块或神经原纤维缠结（nft）的形成。在这里，我们通过体外tau聚集模式、tau过表达的神经细胞系（N2a）和tau过表达的小鼠模型来研究Al是否可能参与NFT的形成。尽管在肝素诱导的tau蛋白组装试验中，Al诱导tau蛋白聚集，但这些聚集物既不是硫黄素T阳性，也不类似于在人类AD大脑中看到的tau蛋白原纤维。对于过表达tau的稳定细胞系的细胞裂解物，当裂解物用至少100 muM Al-maltolate处理时，sds不溶性tau的积累增加。然而，早在大脑中的Al浓度达到100 muM之前，麦芽糖酸铝就会在过度表达人tau的转基因小鼠和非转基因幼崽中引起疾病或死亡。这些结果表明，Al与AD病理无直接联系。
Etiological studies suggest that aluminum (Al) intake might increase an individual's risk of developing Alzheimer's disease (AD). Biochemical analysis data on the effects of Al, however, are inconsistent. Hence, the pathological involvement of Al in AD remains unclear. If Al is involved in AD, then it is reasonable to hypothesize that Al might be involved in the formation of either amyloid plaques or neurofibrillary tangles (NFTs). Here, we investigated whether Al might be involved in NFT formation by using an in vitro tau aggregation paradigm, a tau-overexpressing neuronal cell line (N2a), and a tau-overexpressing mouse model. Although Al induced tau aggregation in a heparin-induced tau assembly assay, these aggregates were neither thioflavin T positive nor did they resemble tau fibrils seen in human AD brains. With cell lysates from stable cell lines overexpressing tau, the accumulation of SDS-insoluble tau increased when the lysates were treated with at least 100 muM Al-maltolate. Yet Al-maltolate caused illness or death in transgenic mice overexpressing human tau and in non-transgenic littermates well before the Al concentration in the brain reached 100 muM. These results indicate that Al has no direct link to AD pathology.