Elevation of brain glucose and polyol-pathway intermediates with accompanying brain-copper deficiency in patients with Alzheimer's disease: metabolic basis for dementia.
Elevation of brain glucose and polyol-pathway intermediates with accompanying brain-copper deficiency in patients with Alzheimer's disease: metabolic basis for dementia.
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DOI：
10.1038/srep27524
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发表时间：
2016-06-09
影响因子：
4.6
通讯作者：
Cooper GJ
中科院分区：
文献类型：
--
作者：
Xu J;Begley P;Church SJ;Patassini S;McHarg S;Kureishy N;Hollywood KA;Waldvogel HJ;Liu H;Zhang S;Lin W;Herholz K;Turner C;Synek BJ;Curtis MA;Rivers-Auty J;Lawrence CB;Kellett KA;Hooper NM;Vardy ER;Wu D;Unwin RD;Faull RL;Dowsey AW;Cooper GJ
阿尔茨海默病（AD）患者脑葡萄糖摄取和脑铜调节功能受损。在这里，我们试图通过测量经历不同程度损伤的大脑区域中代谢物和金属的水平，进一步阐明导致AD神经退行性变的过程。我们采用质谱法（MS）来测量代谢物和金属在7个死后的大脑区域的9个AD患者和9个控制，和血浆葡萄糖和血浆铜水平在一个死前的病例对照研究。葡萄糖、山梨糖醇和果糖在所有AD脑区均显著升高，而铜在整个脑区均相应缺乏（所有P < 0.0001）。相反，在死亡前病例对照研究中，患者和对照组之间的血糖和血浆铜水平没有差异。AD脑组织中葡萄糖和铜的调节普遍存在缺陷，但没有证据表明血浆中存在相应的全身异常。脑葡萄糖升高和脑铜缺乏可能有助于AD神经退行性变的发病机制。
Impairment of brain-glucose uptake and brain-copper regulation occurs in Alzheimer’s disease (AD). Here we sought to further elucidate the processes that cause neurodegeneration in AD by measuring levels of metabolites and metals in brain regions that undergo different degrees of damage. We employed mass spectrometry (MS) to measure metabolites and metals in seven post-mortem brain regions of nine AD patients and nine controls, and plasma-glucose and plasma-copper levels in an ante-mortem case-control study. Glucose, sorbitol and fructose were markedly elevated in all AD brain regions, whereas copper was correspondingly deficient throughout (all P < 0.0001). In the ante-mortem case-control study, by contrast, plasma-glucose and plasma-copper levels did not differ between patients and controls. There were pervasive defects in regulation of glucose and copper in AD brain but no evidence for corresponding systemic abnormalities in plasma. Elevation of brain glucose and deficient brain copper potentially contribute to the pathogenesis of neurodegeneration in AD.