Paired plasma lipidomics and proteomics analysis in the conversion from mild cognitive impairment to Alzheimer's disease
Gómez-Pascual, A. (Steno Diabetes Center Copenhagen)
Xu, J. (King's College London)
Wretlind, A. (Steno Diabetes Center Copenhagen)
Shi, L. (Novo Nordisk Research Centre Oxford (NNRCO))
Buckley, Noel J. (Kavli Institute for Nanoscience Discovery)
Tijms, Betty M. (Amsterdam UMC)
Vos, Stephanie J.B. (Maastricht University)
Engelborghs, Sebastiaan (Vrije Universiteit Brussel)
Sleegers, Kristel (University of Antwerp)
Wallin, Anders (Sahlgrenska Academy at University of Gothenburg)
Lleó, Alberto (Institut de Recerca Sant Pau)
Popp, Julius (University of Zürich)
Martinez-Lage, P. (Fundación CITA-Alzhéimer Fundazioa (San Sebastián, País Basc))
Streffer, J. (AC Immune SA. formerly Janssen R&D. LLC. Beerse. Belgium at the time of study conduct)
Barkhof, Frederik (University College London)
Zetterberg, Henrik (University College London. Institute of Neurology)
Visser, Pieter Jelle (Maastricht University)
Lovestone, Simon (Janssen Medical (UK))
Bertram, Lars (University of Oslo)
Nevado-Holgado, Alejo (University of Oxford)
Proitsi, Petroula (King's College London)
Botía, Juan A. (Universidad de Murcia)
Legido-Quigley, Cristina (King's College London)
Naccache, Talel (City University of London)
Hooshmand, Kourosh (Steno Diabetes Center Copenhagen)
Gabrielli, Martina (CNR Institute of Neuroscience)
Lombardo, Marta Tiffany (University of Milano-Bicocca)
ten Kate, Mara (Amsterdam UMC)
Frisoni, Giovanni B. (IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli (Brescia, Itàlia))
Gualerzi, Alice (IRCCS Fondazione Don Carlo Gnocchi ONLUS in Milan)
Picciolini, Silvia (IRCCS Fondazione Don Carlo Gnocchi ONLUS in Milan)
Verderio, Claudia (CNR Institute of Neuroscience)
Universitat Autònoma de Barcelona. Departament de Medicina

Data:	2024
Resum:	Background: Alzheimer's disease (AD) is a neurodegenerative condition for which there is currently no available medication that can stop its progression. Previous studies suggest that mild cognitive impairment (MCI) is a phase that precedes the disease. Therefore, a better understanding of the molecular mechanisms behind MCI conversion to AD is needed. Method: Here, we propose a machine learning-based approach to detect the key metabolites and proteins involved in MCI progression to AD using data from the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery Study. Proteins and metabolites were evaluated separately in multiclass models (controls, MCI and AD) and together in MCI conversion models (MCI stable vs converter). Only features selected as relevant by 3/4 algorithms proposed were kept for downstream analysis. Results: Multiclass models of metabolites highlighted nine features further validated in an independent cohort (0. 726 mean balanced accuracy). Among these features, one metabolite, oleamide, was selected by all the algorithms. Further in-vitro experiments in rodents showed that disease-associated microglia excreted oleamide in vesicles. Multiclass models of proteins stood out with nine features, validated in an independent cohort (0. 720 mean balanced accuracy). However, none of the proteins was selected by all the algorithms. Besides, to distinguish between MCI stable and converters, 14 key features were selected (0. 872 AUC), including tTau, alpha-synuclein (SNCA), junctophilin-3 (JPH3), properdin (CFP) and peptidase inhibitor 15 (PI15) among others. Conclusions: This omics integration approach highlighted a set of molecules associated with MCI conversion important in neuronal and glia inflammation pathways.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Alzheimer's disease ; Integrative omics ; Machine learning ; Metabolomics ; Mild cognitive impairment ; Proteomics
Publicat a:	Computers in Biology and Medicine, Vol. 176 (June 2024) , art. 108588, ISSN 1879-0534

DOI: 10.1016/j.compbiomed.2024.108588
PMID: 38761503

11 p, 1.8 MB

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