Validation of plasma proteomic biomarkers relating to brain amyloid burden in the EMIF-Alzheimer's disease multimodal biomarker discovery cohort
Westwood, Sarah (University of Oxford)
Baird, Alison L (University of Oxford)
Anand, Sneha N. (University of Oxford)
Nevado-Holgado, Alejo (University of Oxford)
Kormilitzin, Andrey (University of Oxford)
Shi, Liu (University of Oxford)
Hye, Abdul (King's College London)
Ashton, Nicholas J (University of Gothenburg)
Morgan, Angharad R. (Cardiff University)
Bos, Isabelle (Maastricht University)
Vos, Stephanie J.B. (Maastricht University)
Baker, Susan (Janssen R and D)
Buckley, Noel J (University of Oxford)
Ten Kate, Mara (Vrije Universiteit University Medical Center)
Scheltens, Philip (Vrije Universiteit University Medical Center)
Teunissen, Charlotte E. (Vrije Universiteit University Medical Center)
Vandenberghe, Rik (University Hospitals Leuven (Bèlgica))
Gabel, Silvy (Ku Leuven)
Meersmans, Karen (Ku Leuven)
Engelborghs, Sebastiaan (Vrije Universiteit Brussel (VUB))
De Roeck, Ellen E. (Vrije Universiteit Brussel (VUB))
Sleegers, Kristel (Center for Molecular Neurology)
Frisoni, Giovanni B. (Irccs Istituto Centro San Giovanni di Dio Fatebenefratelli)
Blin, Olivier (Aix-Marseille Université)
Richardson, Jill C. (GlaxoSmithKline R and D)
Bordet, Régis (University of Lille)
Molinuevo, José Luis (Hospital Clínic i Provincial de Barcelona)
Rami, Lorena (Universitat Pompeu Fabra)
Wallin, Anders (Sahlgrenska Academy at University of Gothenburg)
Kettunen, Petronella (Sahlgrenska Academy at University of Gothenburg)
Tsolaki, Magda (AHEPA University Hospital (Grècia))
Verhey, Frans (Maastricht University)
Lleó, Alberto (Institut d'Investigació Biomèdica Sant Pau)
Sala, Isabel (Institut d'Investigació Biomèdica Sant Pau)
Popp, Julius (Geneva University Hospitals)
Peyratout, Gwendoline (Lausanne University Hospital)
Martinez-Lage, Pablo (Geneva University Hospitals)
Tainta, Mikel (CITA-Alzheimer Foundation)
Johannsen, Peter (Copenhagen University Hospital)
Freund-Levi, Yvonne (Karolinska Institutet (Estocolm, Suècia))
Frölich, Lutz (University of Heidelberg)
Dobricic, Valerija (University of Lübeck)
Legido-Quigley, Cristina (Steno Diabetes Center)
Bertram, Lars (University of Oslo)
Barkhof, Frederik (Ucl Institutes of Neurology and Healthcare Engineering)
Zetterberg, Henrik (Ucl Institute of Neurology)
Morgan, B.Paul (Cardiff University)
Streffer, Johannes (Janssen R and D. Llc)
Visser, Pieter Jelle (Vu University Medical Center)
Lovestone, Simon (Janssen R and D)
Universitat Autònoma de Barcelona

Fecha:	2020
Resumen:	We have previously investigated, discovered, and replicated plasma protein biomarkers for use to triage potential trials participants for PET or cerebrospinal fluid measures of Alzheimer's disease (AD) pathology. This study sought to undertake validation of these candidate plasma biomarkers in a large, multi-center sample collection. Targeted plasma analyses of 34 proteins with prior evidence for prediction of in vivo pathology were conducted in up to 1,000 samples from cognitively healthy elderly individuals, people with mild cognitive impairment, and in patients with AD-type dementia, selected from the EMIF-AD catalogue. Proteins were measured using Luminex xMAP, ELISA, and Meso Scale Discovery assays. Seven proteins replicated in their ability to predict in vivo amyloid pathology. These proteins form a biomarker panel that, along with age, could significantly discriminate between individuals with high and low amyloid pathology with an area under the curve of 0. 74. The performance of this biomarker panel remained consistent when tested in apolipoprotein E ϵ4 non-carrier individuals only. This blood-based panel is biologically relevant, measurable using practical immunocapture arrays, and could significantly reduce the cost incurred to clinical trials through screen failure.
Derechos:	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, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Alzheimer's disease ; Amyloid-β ; Biomarkers ; Plasma ; Proteomics
Publicado en:	Journal of Alzheimer's disease, Vol. 74 Núm. 1 (2020) , p. 213-225, ISSN 1875-8908

DOI: 10.3233/JAD-190434
PMID: 31985466

13 p, 162.5 KB

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