Plasma metabolite profiles of Alzheimer's disease and mild cognitive impairment.
Previous studies have demonstrated altered metabolites in samples of Alzheimer's disease (AD) patients. However, the sample size from many of them is relatively small and the metabolites are relatively limited. Here we applied a comprehensive platform using ultraperformance liquid chromatography-time-of-flight mass spectrometry and gas chromatography-time-of-flight mass spectrometry to analyze plasma samples from AD patients, amnestic mild cognitive impairment (aMCI) patients, and normal controls. A biomarker panel consisting of six plasma metabolites (arachidonic acid, N,N-dimethylglycine, thymine, glutamine, glutamic acid, and cytidine) was identified to discriminate AD patients from normal control. Another panel of five plasma metabolites (thymine, arachidonic acid, 2-aminoadipic acid, N,N-dimethylglycine, and 5,8-tetradecadienoic acid) was able to differentiate aMCI patients from control subjects. Both biomarker panels had good agreements with clinical diagnosis. The 2 panels of metabolite markers were all involved in fatty acid metabolism, one-carbon metabolism, amino acid metabolism, and nucleic acid metabolism. Additionally, no altered metabolites were found among the patients at different stages, as well as among those on anticholinesterase medication and those without anticholinesterase medication. These findings provide a comprehensive global plasma metabolite profiling and may contribute to making early diagnosis as well as understanding the pathogenic mechanism of AD and aMCI.
Department of Neurology and Institute of Neurology, Rui Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine , Shanghai 200025, China.
Gang
G
Wang
Yi
Y
Zhou
Feng-Jie
FJ
Huang
Hui-Dong
HD
Tang
Xu-Hua
XH
Xu
Jia-Jian
JJ
Liu
Ying
Y
Wang
Yu-Lei
YL
Deng
Ru-Jing
RJ
Ren
Wei
W
Xu
Jian-Fang
JF
Ma
Yi-Nan
YN
Zhang
Ai-Hua
AH
Zhao
Sheng-Di
SD
Chen
Wei
W
Jia
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000175:diagnosis / Q000378:metabolism*; D016718:Arachidonic Acid / Q000097:blood; D015415:Biomarkers / Q000097:blood / Q000378:metabolism*; D002853:Chromatography, Liquid; D060825:Cognitive Dysfunction / Q000097:blood / Q000175:diagnosis / Q000378:metabolism*; D003562:Cytidine / Q000097:blood; D008401:Gas Chromatography-Mass Spectrometry; D018698:Glutamic Acid / Q000097:blood; D005973:Glutamine / Q000097:blood; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D015203:Reproducibility of Results; D012521:Sarcosine / Q000031:analogs & derivatives / Q000097:blood; D012680:Sensitivity and Specificity; D013941:Thymine / Q000097:blood
D015415:Biomarkers; D005973:Glutamine; D016718:Arachidonic Acid; D018698:Glutamic Acid; D003562:Cytidine; C025138:dimethylglycine; D013941:Thymine; D012521:Sarcosine