Multi-dimensional mass spectrometry-based shotgun lipidomics and the altered lipids at the mild cognitive impairment stage of Alzheimer's disease.

Multi-dimensional mass spectrometry-based shotgun lipidomics and the altered lipids at the mild cognitive impairment stage of Alzheimer's disease.
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DOI:
10.1016/j.bbalip.2010.01.010
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发表时间:
2010-08
期刊:
Biochimica et biophysica acta
影响因子:
--
通讯作者:
Han X
Han X
中科院分区:
其他
文献类型:
--
作者:
Han X

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基于多维质谱的鸟枪脂质组学(MDMS-SL)是一种成熟的用于全局脂质分析的技术,其直接从生物样品的脂质提取物中鉴定和定量单个脂质分子种类。通过使用这种技术,我们已经揭示了三个显着的变化,脂质在受试者的大脑样本轻度认知障碍的阿尔茨海默病,包括硫,神经酰胺,和缩醛磷脂。使用MDMS-SL的进一步研究使我们确定了在疾病状态下改变脂质的潜在生化机制,在这篇小型综述中对此进行了深入讨论。具体而言,在研究中,以确定在阿尔茨海默氏病的轻度认知障碍阶段的硫苷脂消耗的原因,我们发现,载脂蛋白E与硫苷脂运输和介导的神经系统中的硫苷脂稳态通过脂蛋白代谢途径,在载脂蛋白E介导的硫苷脂运输的改变可以导致脑中的硫苷脂消耗。总的来说,从脑样本的脂质组学分析获得的结果提供了重要的见解,阿尔茨海默病的发病机制的生化机制。
Multi-dimensional mass spectrometry-based shotgun lipidomics (MDMS-SL) is a well-developed technology for global lipid analysis, which identifies and quantifies individual lipid molecular species directly from lipid extracts of biological samples. By using this technology, we have revealed three marked changes of lipids in brain samples of subjects with mild cognitive impairment of Alzheimer’s disease including sulfatides, ceramides, and plasmalogens. Further studies using MDMS-SL lead us to the identification of the potential biochemical mechanisms responsible for the altered lipids at the disease state, which are thoroughly discussed in this mini review. Specifically, in studies to identify the causes responsible for sulfatide depletion at the mild cognitive impairment stage of Alzheimer’s disease, we have found that apolipoprotein E is associated with sulfatide transport and mediates sulfatide homeostasis in the nervous system through lipoprotein metabolism pathways and that alterations in apolipoprotein E-mediated sulfatide trafficking can lead to sulfatide depletion in the brain. Collectively, the results obtained from lipidomic analyses of brain samples provide important insights into the biochemical mechanisms underlying the pathogenesis of Alzheimer’s disease.
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