Plasmalogen deficiency in early Alzheimer's disease subjects and in animal models: molecular characterization using electrospray ionization mass spectrometry
Plasmalogen deficiency in early Alzheimer's disease subjects and in animal models: molecular characterization using electrospray ionization mass spectrometry
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DOI：
10.1046/j.1471-4159.2001.00332.x
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发表时间：
2001-05-01
影响因子：
4.7
通讯作者：
McKeel, DW
中科院分区：
文献类型：
--
作者：
Han, XL;Holtzman, DM;McKeel, DW
为了探讨乙醇胺型缩醛磷脂的改变可能与阿尔茨海默病（AD）痴呆的严重程度直接相关的假设，我们使用电喷雾电离质谱（ESI/MS）对来自不同区域的人类受试者的灰色和白色物质的细胞膜中的缩醛磷脂含量进行了系统的检查，这些受试者具有AD临床痴呆等级（CDR）谱。结果表明：（1）血浆酶原含量急剧下降在AD的非常早期阶段，白色物质中的（高达总缩醛磷脂的40 mol%）（即CDR 0.5）;（2）灰质血浆酶原含量的缺乏与AD CDR的相关性（即，类似于CDR 0.5处10摩尔%的缺陷（非常轻度痴呆）至类似于CDR 3处30摩尔%的缺陷（严重痴呆）;（3）尽管小脑白色物质中的缩醛磷脂含量显著改变，但在任何CDR处小脑灰质中的缩醛磷脂含量和分子种类没有改变。在两个小鼠模型的AD，应用程序（V717 F）和APPsw，乙醇胺缩醛含量的变化也进行了检查，通过ESI/MS。缩醛缺乏症是目前（10摩尔%的总缩醛在18个月的年龄）在大脑皮层，但在小脑从两个动物模型中是不存在的。这些结果表明，在AD的发病机制中，特别是在白色物质中，缩醛磷脂缺乏可能发挥重要作用，并表明，改变缩醛磷脂含量可能有助于AD的神经变性，突触丢失和突触功能障碍。
To explore the hypothesis that alterations in ethanolamine plasmalogen may be directly related to the severity of dementia in Alzheimer's disease (AD), we performed a systematic examination of plasmalogen content in cellular membranes of gray and white matter from different regions of human subjects with a spectrum of AD clinical dementia ratings (CDR) using electrospray ionization mass spectrometry (ESI/MS). The results demonstrate: (1) a dramatic decrease in plasmalogen content (up to 40 mol% of total plasmalogen) in white matter at a very early stage of AD (i.e. CDR 0.5); (2) a correlation of the deficiency in gray matter plasmalogen content with the AD CDR (i.e. similar to 10 mol% of deficiency at CDR 0.5 (very mild dementia) to similar to 30 mol% of deficiency at CDR 3 (severe dementia); (3) an absence of alterations of plasmalogen content and molecular species in cerebellar gray matter at any CDR despite dramatic alterations of plasmalogen content in cerebellar white matter. Alterations of ethanolamine plasmalogen content in two mouse models of AD, App(V717F) and APPsw, were also examined by ESI/MS. A plasmalogen deficiency was present (up to 10 mol% of total plasmalogen at the age of 18 months) in cerebral cortices, but was absent in cerebella from both animal models. These results suggest plasmalogen deficiency may play an important role in the AD pathogenesis, particularly in the white matter, and suggest that altered plasmalogen content may contribute to neurodegeneration, synapse loss and synaptic dysfunction in AD.