Plasma Metabolite Profiles Of Alzheimer’s Disease And Mild Cognitive Impairment

Objective: Alzheimer’s disease (AD) is a common neurodegenerative disease in theaging population. Early diagnosis and intervention were of great significance forimproving the life of AD patients. As closely related to AD, amnestic mild cognitiveimpairment (aMCI), is also facing difficulties in diagnosis. Metabolomics is an emergingprofiling method of discovering novel biomarkers and understanding the mechanisticpathways underlying a pathophysiological state. Therefore, we aimed to identify a distinctmetabolomics profile and specific plasma biomarkers for the early diagnosis of AD andaMCI through this methodology.Methods: Total57patients with AD,58patients with aMCI and57normal controlswere recruited in our study. Fasting venous blood was collected from all the participantsand phenotyping of APOEε4was performed by Polymerase Chain Reaction-restrictionfragment length polymorphism assays (PCR-RELP). We applied a comprehensiveplatforms using ultra performance liquid chromatography-time of flight-massspectrometry (UPLC-MS) and gas chromatography-time-of-flight mass spectrometry(GC-TOFMS) to analyze plasma samples from AD patients, aMCI patients and normalcontrols. ROC analysis and logistic regression were used to disclose the most qualifiedmetabolic candidate in order to explore simplified biomarker panels for diagnosis of ADand aMCI.Results: A biomarker panel consisting of6plasma metabolites (arachidonic acid, N,N-dimethylglycine, thymine, glutamine, glutamic acid and cytidine) was identified todiscriminate AD patients from normal control. Another panel of5plasma metabolites(thymine, arachidonic acid,2-aminoadipic acid, N,N-dimethylglycine and5,8-tetradecadienoic acid) was able to differentiate aMCI patients from control subjects.Both biomarker panels had good agreements with clinical diagnosis. The2panels ofmetabolite markers were all involved in fatty acid metabolism, one-carbon metabolism,amino-acid and nucleic acid metabolism. Additionally, no altered metabolites were foundamong the patients at different stages, and between those on anticholinesterase medicationand those without anticholinesterase medication.Conclusion: In conclusion, we identified comprehensive metabolic shifts in AD andaMCI subjects including altered fatty acid metabolism, amino acid metabolism,carbohydrate metabolism, and TCA cycle. It also appeared that both AD and aMCIinduced significant metabolic alterations, including energy metabolism and oxidativestress with interactions between hypoxia and mitochondrial dysfunction, and dysfunctionsof Glutamate/Glutamine Cycle and Protein Oxidation.