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.