Plasma Protein Biomarkers for the Prediction of CSF Amyloid and Tau and [ 18 F]-Flutemetamol PET Scan Result
Westwood, Sarah (University of Oxford. Department of Psychiatry)
Baird, Alison L. (Department of Psychiatry, University of Oxford)
Hye, Abdul (NIHR Biomedical Research Centre for Mental Health (Londres, Regne Unit))
Ashton, Nicholas J. (University of Gothenburg)
Nevado-Holgado, Alejo (Department of Psychiatry, University of Oxford)
Anand, Sneha N. (Department of Psychiatry, University of Oxford)
Liu, Benjamine (Department of Psychiatry, University of Oxford)
Newby, Danielle (Department of Psychiatry, University of Oxford)
Bazenet, Chantal (King's College London. Institute of Psychiatry, Psychology & Neuroscience)
Kiddle, Steven J. (MRC Biostatistics Unit, Cambridge Biomedical Campus, Cambridge Institute of Public Health, University of Cambridge)
Ward, Malcolm (King's College London. Institute of Psychiatry, Psychology & Neuroscience)
Newton, Ben (GE Healthcare Life Sciences Core Imaging)
Desai, Keyur (Biosciences, GE Global Research)
Tan Hehir, Cristina (Biosciences, GE Global Research)
Zanette, Michelle (GE Healthcare Life Sciences Core Imaging)
Galimberti, Daniela (Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico)
Parnetti, Lucilla (Center for Memory Disorders and Laboratory of Clinical Neurochemistry, Neurology Clinic, University of Perugia)
Lleó, Alberto (Institut d'Investigació Biomèdica Sant Pau)
Baker, Susan (Janssen Neuroscience Research & Development)
Narayan, Vaibhav A. (Janssen Neuroscience Research & Development)
van der Flier, Wiesje M. (Department of Epidemiology and Biostatistics, VU University Medical Center)
Scheltens, Philip (Amsterdam Universitair Medische Centra (Amsterdam, Països Baixos))
Teunissen, Charlotte E. (Department of Clinical Chemistry, Neurochemistry Lab and Biobank, Amsterdam Neuroscience, VU University Medical Center)
Visser, Pieter Jelle (Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University)
Lovestone, Simon (Department of Psychiatry, University of Oxford)
Universitat Autònoma de Barcelona

Date:	2018
Abstract:	Background: Blood biomarkers may aid in recruitment to clinical trials of Alzheimer's disease (AD) modifying therapeutics by triaging potential trials participants for amyloid positron emission tomography (PET) or cerebrospinal fluid (CSF) Aβ and tau tests. Objective: To discover a plasma proteomic signature associated with CSF and PET measures of AD pathology. Methods: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) based proteomics were performed in plasma from participants with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and AD, recruited to the Amsterdam Dementia Cohort, stratified by CSF Tau/Aβ (n = 50). Technical replication and independent validation were performed by immunoassay in plasma from SCD, MCI, and AD participants recruited to the Amsterdam Dementia Cohort with CSF measures (n = 100), MCI participants enrolled in the GE067-005 study with [ 18 F]-Flutemetamol PET amyloid measures (n = 173), and AD, MCI and cognitively healthy participants from the EMIF 500 study with CSF Aβ measurements (n = 494). Results: 25 discovery proteins were nominally associated with CSF Tau/Aβ (P < 0. 05) with associations of ficolin-2 (FCN2), apolipoprotein C-IV and fibrinogen β chain confirmed by immunoassay (P < 0. 05). In the GE067-005 cohort, FCN2 was nominally associated with PET amyloid (P < 0. 05) replicating the association with CSF Tau/Aβ. There were nominally significant associations of complement component 3 with PET amyloid, and apolipoprotein(a), apolipoprotein A-I, ceruloplasmin, and PPY with MCI conversion to AD (all P < 0. 05). In the EMIF 500 cohort FCN2 was trending toward a significant relationship with CSF Aβ (P ≈ 0. 05), while both A1AT and clusterin were nominally significantly associated with CSF Aβ (both P < 0. 05). Conclusion: Associations of plasma proteins with multiple measures of AD pathology and progression are demonstrated. To our knowledge this is the first study to report an association of FCN2 with AD pathology. Further testing of the proteins in larger independent cohorts will be important. Department of Psychiatry.
Rights:	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.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	Frontiers in aging neuroscience, Vol. 10 (december 2018) , ISSN 1663-4365

DOI: 10.3389/fnagi.2018.00409
PMID: 30618716

15 p, 1.2 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles