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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Vydáno v:	Scientific reports Ročník 10; číslo 1; s. 21745 - 17
Hlavní autoři:	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
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 10.12.2020 Nature Publishing Group Nature Portfolio
Témata:	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
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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 PMCID: PMC7730184
ISSN:	2045-2322 2045-2322
DOI:	10.1038/s41598-020-78031-9