Replication study of plasma proteins relating to Alzheimer's pathology
Shi, Liu (University of Oxford. Department of Psychiatry)
Winchester, Laura M. (University of Oxford. Department of Psychiatry)
Westwood, Sarah (University of Oxford. Department of Psychiatry)
Baird, Alison L (University of Oxford. Department of Psychiatry)
Anand, Sneha N (University of Oxford. Department of Psychiatry)
Buckley, Noel J. (University of Oxford. Department of Psychiatry)
Hye, Abdul (Maurice Wohl Clinical Neuroscience. Institute of Psychiatry. Psychology and Neuroscience. Kings College London)
Ashton, Nicholas J. (University of Gothenburg)
Bos, Isabelle (Alzheimer Center. VU University Medical Center)
Vos, Stephanie J.B. (Maastricht University. School for Mental Health and Neuroscience)
Kate, Mara Ten (Amsterdam UMC. University Medical Center)
Scheltens, Philip (Amsterdam UMC. University Medical Center)
Teunissen, Charlotte E. (Amsterdam University Medical Centers (AUMC))
Vandenberghe, Rik (University Hospitals Leuven (Bèlgica))
Gabel, Silvy (KU Leuven. Laboratory for Cognitive Neurology)
Meersmans, Karen (KU Leuven. Laboratory for Cognitive Neurology)
Engelborghs, Sebastiaan (Department of Neurology. UZ Brussel and Center for Neurociences (C4N). Vrije Universiteit Brussel)
De Roeck, Ellen E (Department of Neurology and Memory Clinic. Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken)
Sleegers, Kristel (University of Antwerp. Institute Born-Bunge)
Frisoni, Giovanni B. (IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli)
Blin, Olivier (AIX marseille university. INS. Ap-hm)
Richardson, Jill C. (Neurosciences Therapeutic Area. GlaxoSmithKline R&D)
Bordet, Régis (Inserm. University of Lille. CHU Lille)
Molinuevo, José Luis (Barcelonaβeta Brain Research Center (BBRC))
Rami Gonzalez, Lorena (Barcelonaβeta Brain Research Center (BBRC))
Wallin, Anders (Institute of Neuroscience and Physiology. Sahlgrenska Academy at University of Gothenburg)
Kettunen, Petronella (Institute of Neuroscience and Physiology. Sahlgrenska Academy at University of Gothenburg)
Tsolaki, Magda (AHEPA University Hospital (Grècia))
Verhey, Frans (Maastricht University. School for Mental Health and Neuroscience)
Lleó, Alberto (Institut d'Investigació Biomèdica Sant Pau)
Sala, Isabel (Institut d'Investigació Biomèdica Sant Pau)
Popp, Julius (Geriatric Psychiatry. Department of Mental Health and Psychiatry. Geneva University Hospitals)
Peyratout, Gwendoline (Lausanne University Hospital)
Martinez-Lage, Pablo (CITA-Alzheimer Foundation)
Tainta, Mikel (CITA-Alzheimer Foundation)
Johannsen, Peter (Danish Dementia Research Centre. Rigshospitalet. Copenhagen University Hospital)
Freund-Levi, Yvonne (Karolinska Institutet Center for Alzheimer Research. Division of Clinical Geriatrics. School of Medical Sciences Örebro University and Department of Neurobiology. Caring Sciences and Society (NVS))
Frölich, Lutz (Department of Geriatric Psychiatry. Zentralinstitut für Seelische Gesundheit. University of Heidelberg)
Dobricic, Valerija (Lübeck Interdisciplinary Platform for Genome Analytics. Institutes of Neurogenetics and Cardiogenetics. University of Lübeck)
Legido-Quigley, Cristina (The Systems Medicine Group. Steno Diabetes Center)
Barkhof, Frederik (UCL Institutes of Neurology and Healthcare Engineering)
Andreasson, Ulf (Clinical Sahlgrenska University Hospital)
Blennow, Kaj (Sahlgrenska University Hospital (Suècia))
Zetterberg, Henrik (UCL Institute of Neurology (Regne Unit))
Streffer, Johannes (UCB. Braine-l'Alleud. Belgium. formerly Janssen R&D. LLC Beerse)
Lill, Christina M. (Ageing Epidemiology Research Unit. School of Public Health. Imperial College)
Bertram, Lars (Department of Psychology. University of Oslo)
Visser, Pieter Jelle (Alzheimer Center. VU University Medical Center)
Kolb, Hartmuth C. (Janssen R&D)
Narayan, Vaibhav A. (Janssen R&D)
Lovestone, Simon (Janssen R&D)
Nevado-Holgado, Alejo (Department of Psychiatry. University of Oxford)

Fecha:	2021
Resumen:	Introduction: This study sought to discover and replicate plasma proteomic biomarkers relating to Alzheimer's disease (AD) including both the "ATN" (amyloid/tau/neurodegeneration) diagnostic framework and clinical diagnosis. Methods: Plasma proteins from 972 subjects (372 controls, 409 mild cognitive impairment [MCI], and 191 AD) were measured using both SOMAscan and targeted assays, including 4001 and 25 proteins, respectively. Results: Protein co-expression network analysis of SOMAscan data revealed the relation between proteins and "N" varied across different neurodegeneration markers, indicating that the ATN variants are not interchangeable. Using hub proteins, age, and apolipoprotein E ε4 genotype discriminated AD from controls with an area under the curve (AUC) of 0. 81 and MCI convertors from non-convertors with an AUC of 0. 74. Targeted assays replicated the relation of four proteins with the ATN framework and clinical diagnosis. Discussion: Our study suggests that blood proteins can predict the presence of AD pathology as measured in the ATN framework as well as clinical diagnosis.
Ayudas:	European Commission FP7/2007-2013 European Commission QLRT2001-2455 European Commission 37670 European Research Council 681712
Nota:	Altres ajuts: Innovative Medicines Initiative (EMIF grant agreement n° 115372); Stichting voor Alzheimer Onderzoek (grant numbers #11020, #13007, and #15005); Flemish Research Foundation (FWO); Department of Health of the Basque Government (allocation 17.0.1.08.12.0000.2.454.01.41142.001.H); University of Antwerp Research Fund; Swedish Research Council (#2018-02532); Swedish State Support for Clinical Research (#ALFGBG-720931); the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862); UK Dementia Research Institute at UCL; NIHR biomedical research center at UCLH.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Alzheimer's disease ; ATN framework ; Biomarker ; Dementia ; Network analysis ; Plasma proteomics ; Replication
Publicado en:	Alzheimer's & Dementia, Vol. 17 Núm. 9 (september 2021) , p. 1452-1464, ISSN 1552-5279

DOI: 10.1002/alz.12322
PMID: 33792144

13 p, 1.8 MB

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