title: Sphingomyelin SM(d18:1/18:0) is significantly enhanced in cerebrospinal fluid samples dichotomized by pathological amyloid-β42, tau, and phospho-tau-181 levels.
abstract: Alzheimer's disease (AD) is a severe and chronic neurodegenerative disorder of the brain. The laboratory diagnosis is limited to the analysis of three biomarkers in cerebrospinal fluid (CSF): amyloid-β42 (Aβ42), total tau, and phospho-tau-181 (P-tau-181). However, there is a need to find more biomarkers in CSF that can improve the sensitivity and specificity. The aim of the present study was to analyze endogenous small metabolites (metabolome) in the CSF, which may provide potentially new insights into biochemical processes involved in AD. One hundred CSF samples were dichotomized by normal (n = 50) and pathological decreased Aβ42 and increased tau and P-tau-181 levels (n = 50; correlating to an AD-like pathology). These CSF samples were analyzed using the AbsoluteIDQ® p180 Kit (BIOCRATES Life Sciences), which included 40 acylcarnitines, 21 amino acids, 19 biogenic amines, 15 sphingolipids, and 90 glycerophospholipids. Our data show that two sphingomyelins (SM (d18:1/18:0) and SM (d18:1/18:1)), 5 glycerophospholipids (PC aa C32:0, PC aa C34:1, PC aa C36:1, PC aa C38:4 and PC aa C38:6), and 1 acylcarnitine (C3-DC-M/C5-OH) were significantly altered in the CSF with pathological "AD-like pathology". Sphingomyelin SM (d18:1/18:0) proved to be a specific (76%) and sensitive (66%) biomarker with a defined cut-off of 546 nM. Correct diagnoses for 21 out of 32 unknown samples could be achieved using this SM (d18:1/18:0) cut-off value. In conclusion, the sphingolipid SM (d18:1/18:0) is significantly increased in CSF of patients displaying pathological levels of Aβ42, tau, and P-tau-181.
authors.affiliation: BIOCRATES Life Sciences AG, Innsbruck, Austria.
authors.forename: Therese
authors.initials: T
authors.lastname: Koal
authors.affiliation: BIOCRATES Life Sciences AG, Innsbruck, Austria.
authors.forename: Kristaps
authors.initials: K
authors.lastname: Klavins
authors.affiliation: BIOCRATES Life Sciences AG, Innsbruck, Austria.
authors.forename: Daniele
authors.initials: D
authors.lastname: Seppi
authors.affiliation: Department of Psychiatry and Psychotherapy, University Clinic of General and Social Psychiatry, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Georg
authors.initials: G
authors.lastname: Kemmler
authors.affiliation: Department of Psychiatry and Psychotherapy, University Clinic of General and Social Psychiatry, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Humpel
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D010766:Phosphorylation; D013109:Sphingomyelins / Q000134:cerebrospinal fluid*; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D013109:Sphingomyelins; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
keywords: Alzheimer's disease; SM(d18:1/18:0); cerebrospinal fluid; diagnosis; liquor; metabolomics; sphingolipids