Specific changes of sulfatide levels in individuals with pre-clinical Alzheimer's disease: an early event in disease pathogenesis
Specific changes of sulfatide levels in individuals with pre-clinical Alzheimer's disease: an early event in disease pathogenesis
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DOI：
10.1111/jnc.12368
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发表时间：
2013-12-01
影响因子：
4.7
通讯作者：
Han, Xianlin
中科院分区：
文献类型：
--
作者：
Cheng, Hua;Wang, Miao;Han, Xianlin
为了探索细胞膜脂质的改变存在于临床前阿尔茨海默病（AD）阶段（即，死亡时认知正常，但患有AD神经病理学），我们对来自患有临床前AD的受试者的死后脑的脂质提取物进行靶向鸟枪脂质组学。我们发现，与没有AD神经病理学的受试者相比，临床前AD受试者的硫苷脂水平显著降低。我们还发现，在AD的这个阶段，乙醇胺甘油磷脂的水平略低，而神经酰胺水平的变化在现有样本中检测不到。这些结果表明，细胞膜缺陷存在于AD发病机制的最早阶段，也表明，硫苷脂损失是AD发展的最早期事件之一，而乙醇胺甘油磷脂和神经酰胺水平的改变发生在疾病的相对较晚。
To explore the hypothesis that alterations in cellular membrane lipids are present at the stage of pre-clinical Alzheimer's disease (AD) (i.e., cognitively normal at death, but with AD neuropathology), we performed targeted shotgun lipidomics of lipid extracts from post-mortem brains of subjects with pre-clinical AD. We found sulfatide levels were significantly lower in subjects with pre-clinical AD compared to those without AD neuropathology. We also found that the level of ethanolamine glycerophospholipid was marginally lower at this stage of AD, whereas changes of the ceramide levels were undetectable with the available samples. These results indicate that cellular membrane defects are present at the earliest stages of AD pathogenesis and also suggest that sulfatide loss is among the earliest events of AD development, while alterations in the levels of ethanolamine glycerophospholipid and ceramide occur relatively later in disease.