Erythrocyte sphingolipid species as biomarkers of Alzheimer's disease  

作　　者：Jericha Mill Vihar Patel Ozioma Okonkwo Lingjun Li Thomas Raife 

机构地区：[1]Department of Chemistry,University of Wisconsin-Madison,Madison,WI,53706,USA [2]Department of Pathology and Laboratory Medicine,University of Wisconsin School of Medicine and Public Health,Madison,WI,53705,USA [3]Clinical Science Center,Wisconsin Alzheimer's Disease Research Center,University of Wisconsin School of Medicine and Public Health,Madison,WI,53792,USA [4]School of Pharmacy,University of Wisconsin-Madison,Madison,WI,53705,USA

出　　处：《Journal of Pharmaceutical Analysis》2022年第1期178-185,共8页药物分析学报（英文版）

基　　金：supported in part by the National Institutes of Health(NIH)(Grant No.:RF1AG052324);a predoctoral traineeship supported by the NIH T32 training grant on Biology of Aging and Age-related Diseases(Grant No.:T32AG000213);funding provided by the Wisconsin Alumni Research Foundation;School of Pharmacy,University of Wisconsin-Madison

摘　　要：Diagnosing Alzheimer’s disease(AD)in the early stage is challenging.Informative biomarkers can be of great value for population-based screening.Metabolomics studies have been used to find potential biomarkers,but commonly used tissue sources can be difficult to obtain.The objective of this study was to determine the potential utility of erythrocyte metabolite profiles in screening for AD.Unlike some commonly-used sources such as cerebrospinal fluid and brain tissue,erythrocytes are plentiful and easily accessed.Moreover,erythrocytes are metabolically active,a feature that distinguishes this sample source from other bodily fluids like plasma and urine.In this preliminary pilot study,the erythrocyte metabolomes of 10 histopathologically confirmed AD patients and 10 patients without AD(control(CTRL))were compared.Whole blood was collected post-mortem and erythrocytes were analyzed using ultraperformance liquid chromatography tandem mass spectrometry.Over 750 metabolites were identified in AD and CTRL erythrocytes.Seven were increased in AD while 24 were decreased(P<0.05).The majority of the metabolites increased in AD were associated with amino acid metabolism and all of the decreased metabolites were associated with lipid metabolism.Prominent among the potential biomarkers were 10 sphingolipid or sphingolipid-related species that were consistently decreased in AD patients.Sphingolipids have been previously implicated in AD and other neurological conditions.Furthermore,previous studies have shown that erythrocyte sphingolipid concentrations vary widely in normal,healthy adults.Together,these observations suggest that certain erythrocyte lipid phenotypes could be markers of risk for development of AD.

关 键 词：Alzheimer’s disease Neurodegenerative disease Mass spectrometry Erythrocytes Biomarkers Metabolomics 

分 类 号：R749.16[医药卫生—神经病学与精神病学]