Urinary metabolic phenotyping for Alzheimer's disease
File(s)Urinary metabolic phenotyping for Alzheimers disease.pdf (2.07 MB)
Published version
Author(s)
Type
Journal Article
Abstract
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.
Date Issued
2020-12-10
Date Acceptance
2020-11-18
Citation
Scientific Reports, 2020, 10 (21745)
ISSN
2045-2322
Publisher
Nature Publishing Group
Journal / Book Title
Scientific Reports
Volume
10
Issue
21745
Copyright Statement
© The Author(s) 2020
License URL
Sponsor
UK DRI Ltd
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000609195000101&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
4050641385
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
PRIMARY BILIARY-CIRRHOSIS
COGNITIVE IMPAIRMENT
PREGNENOLONE SULFATE
GUT MICROBIOTA
AMYLOID-BETA
MOUSE MODELS
BILE-ACIDS
BIOMARKERS
ASSOCIATION
DISCOVERY
Publication Status
Published
Article Number
ARTN 21745
Date Publish Online
2020-12-10