Urinary metabolic phenotyping for Alzheimer’s disease

Finding early disease markers using non-invasive and widely available methods is essential to develop a successful therapy for Alzheimer’s Disease. Few studies to date have examined urine, the most readily available biofluid. Here we report the largest study to date using comprehensive metabolic phe...

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Bibliographic Details
Published in:Scientific reports Vol. 10; no. 1; pp. 21745 - 17
Main Authors: Kurbatova, Natalja, Garg, Manik, Whiley, Luke, Chekmeneva, Elena, Jiménez, Beatriz, Gómez-Romero, María, Pearce, Jake, Kimhofer, Torben, D’Hondt, Ellie, Soininen, Hilkka, Kłoszewska, Iwona, Mecocci, Patrizia, Tsolaki, Magda, Vellas, Bruno, Aarsland, Dag, Nevado-Holgado, Alejo, Liu, Benjamine, Snowden, Stuart, Proitsi, Petroula, Ashton, Nicholas J., Hye, Abdul, Legido-Quigley, Cristina, Lewis, Matthew R., Nicholson, Jeremy K., Holmes, Elaine, Brazma, Alvis, Lovestone, Simon
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 10.12.2020
Nature Publishing Group
Nature Portfolio
Subjects:
631/61/212
631/61/320
692/53
692/699/375/132
692/699/375/132/1283
Aged
Aged, 80 and over
Alzheimer Disease - genetics
Alzheimer Disease - metabolism
Alzheimer Disease - urine
Alzheimer's disease
amyloid-beta
association
bile-acids
biomarkers
Biomarkers - urine
Cholesterol
Cognitive ability
Cognitive Dysfunction - genetics
Cognitive Dysfunction - metabolism
Cognitive Dysfunction - urine
cognitive impairment
discovery
Female
Gene mapping
Genetic diversity
Genetic variance
gut microbiota
Humanities and Social Sciences
Humans
Life Sciences
Magnetic resonance spectroscopy
Male
Metabolism
Metabolites
Metabolomics
Metabolomics - methods
mouse models
multidisciplinary
Neurodegenerative diseases
Neurosciences
Neurovetenskaper
NMR
Nuclear magnetic resonance
Phenotype
Phenotyping
pregnenolone sulfate
primary biliary-cirrhosis
Quantitative Trait Loci
Santé publique et épidémiologie
Science
Science & Technology - Other Topics
Science (multidisciplinary)
Biomarkers
Metabolomics
Alzheimer's disease
Genomics
Dementia
ISSN:2045-2322, 2045-2322
Online Access:Get full text
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Description
Summary:Finding early disease markers using non-invasive and widely available methods is essential to develop a successful therapy for Alzheimer’s Disease. Few studies to date have examined urine, the most readily available biofluid. Here we report the largest study to date using comprehensive metabolic phenotyping platforms (NMR spectroscopy and UHPLC-MS) to probe the urinary metabolome in-depth in people with Alzheimer’s Disease and Mild Cognitive Impairment. Feature reduction was performed using metabolomic Quantitative Trait Loci, resulting in the list of metabolites associated with the genetic variants. This approach helps accuracy in identification of disease states and provides a route to a plausible mechanistic link to pathological processes. Using these mQTLs we built a Random Forests model, which not only correctly discriminates between people with Alzheimer’s Disease and age-matched controls, but also between individuals with Mild Cognitive Impairment who were later diagnosed with Alzheimer’s Disease and those who were not. Further annotation of top-ranking metabolic features nominated by the trained model revealed the involvement of cholesterol-derived metabolites and small-molecules that were linked to Alzheimer’s pathology in previous studies.
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PMCID: PMC7730184
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-020-78031-9