Erythrocyte sphingolipid species as biomarkers of Alzheimer's disease

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.

Recent Advances in Understanding of Alzheimer’s Disease Progression Through Mass Spectrometry-Based Metabolomics

Alzheimer’s disease(AD)is the leading cause of dementia in the aging population,but despite extensive research,there is no consensus on the biological cause of AD.While AD research is dominated by protein/peptide-centric research based on the amyloid hypothesis,a theory that designates dysfunction in beta-amyloid production,accumulation,or disposal as the primary cause of AD,many studies focus on metabolomics as a means of understanding the biological processes behind AD progression.In this review,we discuss mass spectrometry(MS)-based AD metabolomics studies,including sample type and preparation,mass spectrometry data acquisition strategies,and data analysis,as well as biological insights gleaned from these studies,with the hope of informing future AD metabolomic studies.