The brain lipidomes of subcortical ischemic vascular dementia and mixed dementia
The brain lipidomes of subcortical ischemic vascular dementia and mixed dementia
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DOI：
10.1016/j.neurobiolaging.2014.02.025
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发表时间：
2014-10-01
影响因子：
4.2
通讯作者：
Shui, Guanghou
中科院分区：
文献类型：
--
作者：
Lam, Sin Man;Wang, Yuting;Shui, Guanghou
尽管它是血管性痴呆的主要原因，但皮层下缺血性血管性痴呆（SIVD）的主要致病机制仍不清楚。由于缺乏批准的SIVD治疗药物，迫切需要确定新的治疗靶点。SIVD和混合性痴呆（即SIVD和阿尔茨海默病，MixD）的比较脂质组学分析也可能为痴呆发病机制中神经退行性和血管机制之间可能的相互作用提供新的见解。采用液相色谱-质谱联用技术对非痴呆对照组、SIVD和MixD受试者颞叶皮层白质和灰质脂质体进行了综合分析。详细的分子图谱强调了灰质鞘脂脂酰基链异质性在痴呆中的病理相关性。此外，从对照组到SIVD再到MixD，颞叶皮层灰质中的硫脂和溶二磷脂酸水平逐渐升高。白质磷脂谱显示了SIVD患者对慢性缺血的可能适应性机制（即不饱和度增加）和MixD患者膜降解升高。(C) 2014年作者。Elsevier Inc.出版。版权所有。
Despite its importance as the leading cause of vascular dementia, the primary pathogenic mechanisms in subcortical ischemic vascular dementia (SIVD) have remained elusive. Because of the lack of approved therapeutic agents for SIVD, there is a pressing need to identify novel therapeutic targets. Comparative lipidomic analyses of SIVD and mixed dementia (i.e., SIVD and Alzheimer's disease, MixD) may also confer new insights pertaining to the possible interaction between neurodegenerative and vascular mechanisms in the pathogenesis of dementia. Liquid chromatography coupled to mass spectrometry was used to comprehensively analyze the lipidomes of white and gray matter from the temporal cortex of nondemented controls, SIVD, and MixD subjects. Detailed molecular profiles highlighted the pathologic relevance of gray matter sphingolipid fatty acyl chain heterogeneity in dementia. In addition, the levels of sulfatides and lysobisphosphatidic acids were progressively increased in the temporal cortex gray matter from control to SIVD to MixD. White matter phospholipid profiles indicated possible adaptive mechanisms (i.e., increased unsaturation) to chronic ischemia in SIVD and elevated membrane degradation in MixD. (C) 2014 The Authors. Published by Elsevier Inc. All rights reserved.