bile acids; cheminformatics; exposomics; high-resolution mass spectrometry; liquid chromatography; metabolomics; tau Proteins; Amyloid beta-Peptides; Biomarkers; Humans; tau Proteins/cerebrospinal fluid; Amyloid beta-Peptides/cerebrospinal fluid; Pilot Projects; Disease Progression; Alzheimer Disease/cerebrospinal fluid; Alzheimer Disease/diagnosis; Alzheimer Disease/psychology; Neurodegenerative Diseases; Cognitive Dysfunction/cerebrospinal fluid; Cognitive Dysfunction/diagnosis; Cognitive Dysfunction/psychology; Alzheimers disease; Bile acid; Clinical symptoms; Cognitive impairment; Exposomic; High resolution mass spectrometry; Small molecules; Alzheimer Disease; Cognitive Dysfunction; Chemistry (all); Environmental Chemistry
Abstract :
[en] Alzheimer's disease (AD) is a complex and multifactorial neurodegenerative disease, which is currently diagnosed via clinical symptoms and nonspecific biomarkers (such as Aβ1-42, t-Tau, and p-Tau) measured in cerebrospinal fluid (CSF), which alone do not provide sufficient insights into disease progression. In this pilot study, these biomarkers were complemented with small-molecule analysis using non-target high-resolution mass spectrometry coupled with liquid chromatography (LC) on the CSF of three groups: AD, mild cognitive impairment (MCI) due to AD, and a non-demented (ND) control group. An open-source cheminformatics pipeline based on MS-DIAL and patRoon was enhanced using CSF- and AD-specific suspect lists to assist in data interpretation. Chemical Similarity Enrichment Analysis revealed a significant increase of hydroxybutyrates in AD, including 3-hydroxybutanoic acid, which was found at higher levels in AD compared to MCI and ND. Furthermore, a highly sensitive target LC-MS method was used to quantify 35 bile acids (BAs) in the CSF, revealing several statistically significant differences including higher dehydrolithocholic acid levels and decreased conjugated BA levels in AD. This work provides several promising small-molecule hypotheses that could be used to help track the progression of AD in CSF samples.
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
TALAVERA ANDUJAR, Begona ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Environmental Cheminformatics
MARY, Arnaud ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Neuroinflammation Group
VENEGAS MALDONADO, Carmen Jesica ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine > Molecular and Functional Neurobiology > Team Anne GRÜNEWALD
Cheng, Tiejun; National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, United States
Zaslavsky, Leonid; National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, United States
Bolton, Evan E ; National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, United States
HENEKA, Michael ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Fonds National de la Recherche Luxembourg U.S. Department of Health and Human Services
Funding text :
BTA is part of the “Microbiomes in One Health” PhD training program, which is supported by the PRIDE doctoral research funding scheme (PRIDE/11823097) of the Luxembourg National Research Fund (FNR). CV was funded by an FNR CORE Junior Grant (“NeuroFlame”, C20/BM/14548100). The work of EEB, TC, and LZ was supported by the National Center for Biotechnology Information of the National Library of Medicine (NLM), National Institutes of Health. ELS acknowledges funding support from the Luxembourg National Research Fund (FNR) for project A18/BM/12341006, and MTH acknowledges funding support from the FNR within the PEARL program (FNR/16745220).BTA acknowledges support from Gianfranco Frigerio during sample preparation and advice from Corey Griffith and Lorenzo Favilli during data processing/interpretation. Katyeny Manuela Da Silva is acknowledged for her inputs during the manuscript revision. We thank the Metabolomics Platform of the LCSB for their support with the LC-HRMS analysis and other Environmental Cheminformatics and PubChem team members who contributed to this work indirectly via other collaborative and scientific activities. The target LC-MS BA analysis was performed by the Genome BC Proteomics Centre of the University of Victoria (Canada).BTA acknowledges support from Gianfranco Frigerio during sample preparation and advice from Corey Griffith and Lorenzo Favilli during data processing/interpretation. Katyeny Manuela Da Silva is acknowledged for her inputs during the manuscript revision. We thank the Metabolomics Platform of the LCSB for their support with the LC-HRMS analysis and other Environmental Cheminformatics and PubChem team members who contributed to this work indirectly via other collaborative and scientific activities. The target LC–MS BA analysis was performed by the Genome BC Proteomics Centre of the University of Victoria (Canada).
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