A global HILIC-MS approach to measure polar human cerebrospinal fluid metabolome: Exploring gender-associated variation in a cohort of elderly cognitively healthy subjects

• Published in: Analytica chimica acta Vol. 1037; pp. 327 - 337
• Main Authors: Gallart-Ayala, Héctor, Konz, Ioana, Mehl, Florence, Teav, Tony, Oikonomidi, Aikaterini, Peyratout, Gwendoline, van der Velpen, Vera, Popp, Julius, Ivanisevic, Julijana
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 11.12.2018; Elsevier BV
• Subjects: Aged; Amino acids; Annotations; Body fluids; Brain; Central nervous system; Cerebrospinal fluid; Cerebrospinal Fluid - metabolism; Chromatography, Liquid; Cognitive ability; Cognitive Dysfunction - metabolism; Cohort Studies; Cohort study; CSF; Female; Gender differences; Geriatrics; Glycolysis; Healthy Volunteers; HILIC; Homeostasis; Humans; Liquid chromatography; Male; Mass Spectrometry; Mass spectroscopy; Metabolism; Metabolite identification; Metabolites; Metabolome; Metabolomics; Middle Aged; Neurological diseases; Older people; pH effects; Rangefinding; Sex Characteristics; Taurine; Tricarboxylic acid cycle; Metabolomics; Gender differences; Metabolite identification; HILIC; Cohort study; CSF
• ISSN: 0003-2670; 1873-4324; 1873-4324
• DOI: 10.1016/j.aca.2018.04.002

Cerebrospinal fluid (CSF) is a key body fluid that maintains the homeostasis in central nervous system (CNS). As a biofluid whose content reflects the brain metabolic activity, the CSF has been profiled in the context of neurological diseases to provide novel insights into the disease mechanisms. However, a global high-throughput approach to measure a broad diversity of polar metabolites present in CSF is lacking. Although still perceived as challenging and less reproducible, hydrophilic interaction liquid chromatography (HILIC) has recently evolved to offer the unprecedented coverage capacity of water-soluble metabolome. Here, we present a global HILIC high-resolution mass spectrometry-based (HRMS) approach that combines the profiling in acidic pH ESI (+) and basic pH ESI (−) mode to extend the coverage of CSF polar metabolome. This approach allowed us to annotate and measure a broad range of central carbon metabolites (implicated in glycolysis, TCA cycle, nucleotide, amino acid and fatty acid metabolism) in CSF collected from cognitively healthy elderly volunteers (n = 32), using a single extraction method. Metabolite annotation was achieved using the accurate mass, RT and MS/MS criteria, allowing for the characterization of 146 measurable metabolites. Exploration of characterized individual CSF profiles allowed for a discovery of intriguing gender-associated differences, with significantly higher acylcarnitine levels in men and higher taurine levels women. With this case study, we demonstrate the value of combined HILIC ESI ± HRMS profiling to assess CSF metabolome in clinical research studies. [Display omitted] •Global HILIC-HRMS approach combining acidic ESI (+) and basic ESI (−) mode to measure polar human CSF metabolome.•CSF metabolome characterization using accurate mass, retention time and MS/MS data.•Characterized CSF metabolome covered amino acid, nucleotide and fatty acid metabolism, glycolysis and TCA cycle.•Evalulation of inter-individual variability and gender-associated differences in a cohort of elderly cognitively healthy subjects.