期刊
JOURNAL OF PROTEOME RESEARCH
卷 15, 期 2, 页码 608-618出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jproteome.5b01020
关键词
lipidomics; Alzheimer's disease; metabolomics; lipids; metabolic pathways
资金
- Alzheimer's Association [NIRG-11-203674]
- Wellcome Trust [RG 093735/Z/10/Z]
- ERC [260809]
- Austrian Science Fund (FWF) [J3341] Funding Source: Austrian Science Fund (FWF)
- Austrian Science Fund (FWF) [J 3341] Funding Source: researchfish
- The Francis Crick Institute [10134] Funding Source: researchfish
Alzheimer's disease (AD) is the most common cause of adult dementia. Yet the complete set of molecular changes accompanying this inexorable, neurodegenerative disease remains elusive. Here we adopted an unbiased lipidomics and metabolomics approach to surveying frozen frontal cortex samples from clinically characterized AD patients (n = 21) and age-matched controls (n = 19), revealing marked molecular differences between them. Then, by means of metabolomic pathway analysis, we incorporated the novel molecular information into the known biochemical pathways and compared it with the results of a metabolomics meta analysis of previously published AD research. We found six metabolic pathways of the central metabolism as well as glycerophospholipid metabolism predominantly altered in AD brains. Using targeted metabolomics approaches and MS imaging, we confirmed a marked dysregulation of mitochondrial aspartate metabolism. The altered metabolic pathways were further integrated with clinical data, showing various degrees of correlation with parameters of dementia and AD pathology. Our study highlights specific, altered biochemical pathways in the brains of individuals with AD compared with those of control subjects, emphasizing dysregulation of mitochondrial aspartate metabolism and supporting future venues of investigation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据