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A Multiplexed Urinary Biomarker Panel Has Potential for Alzheimer’s Disease Diagnosis Using Targeted Proteomics and Machine Learning

Hällqvist, Jenny; Pinto, Rui C; Heywood, Wendy E; Cordey, Jonjo; Foulkes, Alexander JM; Slattery, Catherine F; Leckey, Claire A; ... Paterson, Ross W; + view all (2023) A Multiplexed Urinary Biomarker Panel Has Potential for Alzheimer’s Disease Diagnosis Using Targeted Proteomics and Machine Learning. International Journal of Molecular Sciences , 24 (18) , Article 13758. 10.3390/ijms241813758. Green open access

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Abstract

As disease-modifying therapies are now available for Alzheimer’s disease (AD), accessible, accurate and affordable biomarkers to support diagnosis are urgently needed. We sought to develop a mass spectrometry-based urine test as a high-throughput screening tool for diagnosing AD. We collected urine from a discovery cohort (n = 11) of well-characterised individuals with AD (n = 6) and their asymptomatic, CSF biomarker-negative study partners (n = 5) and used untargeted proteomics for biomarker discovery. Protein biomarkers identified were taken forward to develop a high-throughput, multiplexed and targeted proteomic assay which was tested on an independent cohort (n = 21). The panel of proteins identified are known to be involved in AD pathogenesis. In comparing AD and controls, a panel of proteins including MIEN1, TNFB, VCAM1, REG1B and ABCA7 had a classification accuracy of 86%. These proteins have been previously implicated in AD pathogenesis. This suggests that urine-targeted mass spectrometry has potential utility as a diagnostic screening tool in AD.

Type: Article
Title: A Multiplexed Urinary Biomarker Panel Has Potential for Alzheimer’s Disease Diagnosis Using Targeted Proteomics and Machine Learning
Open access status: An open access version is available from UCL Discovery
DOI: 10.3390/ijms241813758
Publisher version: https://doi.org/10.3390/ijms241813758
Language: English
Additional information: Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).
Keywords: Alzheimer’s; urine; machine learning; biomarkers; proteomics; mass spectrometry; diagnosis
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10177374
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