Severe In vivo hyper-homocysteinemia is not associatedwith elevation of amyloid-beta peptides in the Tg2576 mice.
Severe In vivo hyper-homocysteinemia is not associatedwith elevation of amyloid-beta peptides in the Tg2576 mice.
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DOI：
10.3233/jad-2010-100171
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Praticò D
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文献类型：
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作者：
Zhuo JM;Praticò D
由于高同型半胱氨酸血症（HHcy）被认为是阿尔茨海默病（AD）的危险因素，许多研究试图在动物模型中诱导HHcy，以研究其对淀粉样蛋白-β前体（a -β pp）代谢的影响。先前的报道发现，在AD转基因小鼠模型中，通过饲喂富含蛋氨酸的饮食或缺乏维生素b的饮食诱导的HHcy与淀粉样蛋白-β (a β)水平升高有关。然而，在任何这些模型中，没有数据表明饮食干预结合过量蛋氨酸和低水平维生素b对淀粉样蛋白形成的影响。在目前的研究中，我们研究了在AD小鼠模型Tg2576中，既富含蛋氨酸又缺乏叶酸、维生素B6和B12的组合饮食的影响。我们发现，这种饮食治疗7个月后，血浆同型半胱氨酸水平高于150 μM的小鼠出现了严重的HHcy。然而，在饮食处理组和对照组之间，没有检测到大脑中Aβ水平或沉积的差异。western blot结果显示，严重的HHcy也没有改变参与a - β pp代谢的蛋白的稳态水平。这些结果表明，这种联合饮食诱导的严重HHcy不影响体内淀粉样蛋白的形成。
Since hyper-homocysteinemia (HHcy) was recognized as a risk factor for Alzheimer’s disease (AD), many studies tried to induce HHcy in animal models to investigate its effect on amyloid-β protein precursor (AβPP) metabolism. Previous reports found that HHcy induced in AD transgenic mouse models, by either feeding a methionine-enriched diet or vitamin Bs deficient diet, is associated with elevation of amyloid-β (Aβ) levels. However, there is no data available on the effect of dietary intervention which combines both excessive methionine and low levels of vitamin Bs on amyloidogenesis in any of these models. In the current study, we investigated the effect of a combination diet, which was both enriched in methionine and deficient in folate, vitamin B6 and B12, in an AD mouse model, the Tg2576. We found that 7 months treatment of this diet induced severe HHcy in these mice with plasma homocysteine level higher than 150 μM. However, no difference was detected in brain Aβ levels or deposition between the diet-treated and control group. As shown by western blot, severe HHcy did not alter the steady state levels of proteins involved in AβPP metabolism, either. These results demonstrate that this combination diet-induced severe HHcy does not influence amyloidogenesis in vivo.