Acceleration of brain amyloidosis in an Alzheimer's disease mouse model by a folate, vitamin B6 and B12-deficient diet.
Acceleration of brain amyloidosis in an Alzheimer's disease mouse model by a folate, vitamin B6 and B12-deficient diet.
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DOI：
10.1016/j.exger.2009.12.005
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发表时间：
2010-03
影响因子：
3.9
通讯作者：
Pratico, Domenico
中科院分区：
文献类型：
--
作者：
Zhuo, Jia-Min;Pratico, Domenico
流行病学和临床研究表明，循环同型半胱氨酸（Hcy）水平升高是阿尔茨海默病（AD）的危险因素。叶酸、维生素B6和B12的饮食缺乏导致Hcy水平显著升高，这种情况也称为高同型半胱氨酸血症（HHcy）。在本研究中，我们测试了这三个重要因素的饮食不足时，给药到AD的小鼠模型，即Tg 2576，将导致高同型半胱氨酸和在其淀粉样变性表型的加速的假设。与正常饮食的Tg 2576小鼠相比，接受叶酸、B6和B12缺乏饮食的小鼠发展了HHcy。这种情况与皮质和海马中Aβ水平的显著增加以及相同区域中Aβ沉积的升高有关。在患有HHcy的小鼠脑中，未观察到总APP、BACE-1、ADAM-10、PS1和nicastrin的稳态水平的显著变化。未观察到主要Aβ分解代谢途径（即IDE和脑啡肽酶蛋白或Aβ伴侣载脂蛋白E）的差异。我们的研究结果表明，导致HHcy的饮食条件也可能导致AD样淀粉样变性转基因小鼠模型中Aβ水平和沉积增加。他们进一步支持的概念，饮食因素可以有助于AD神经病理学的发展。
Epidemiological and clinical studies indicate that elevated circulating level of homocysteine (Hcy) is a risk factor for developing Alzheimer's disease (AD). Dietary deficiency of folate, vitamin B6 and B12 results in a significant increase of Hcy levels, a condition also known as hyperhomocysteinemia (HHcy). In the present study we tested the hypothesis that a diet deficient for these three important factors when administered to a mouse model of AD, i.e. Tg2576, will result in HHcy and in an acceleration of their amylodotic phenotype. Compared with Tg2576 mice on regular chow, the ones receiving the diet-deficient for folate, B6 and B12 developed HHcy. This condition was associated with a significant increase in Aβ levels in the cortex and hippocampus, and an elevation of Aβ deposits in the same regions. No significant changes were observed for steady state levels of total APP, BACE-1, ADAM-10, PS1 and nicastrin in the brains of mice with HHcy. No differences were observed for the main Aβ catabolic pathways, i.e IDE and neprilysin proteins, or the Aβ chaperone apolipoprotein E. Our findings demonstrate that a dietary condition which leads to HHcy may also result in increased Aβ levels and deposition in a transgenic mouse model of AD-like amylodosis. They further support the concept that dietary factors can contribute to the development of AD neuropathology.
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影响因子：
3.3
作者：
Leblhuber, F;Walli, J;Fuchs, D
通讯作者：
Fuchs, D
影响因子：
3.5
作者：
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4.2
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Mayeux, Richard
影响因子：
3.5
作者：
Fuso, Andrea;Nicolia, Vincenzina;Scarpa, Sigfrido
通讯作者：
Scarpa, Sigfrido