Discovery and validation of plasma proteomic biomarkers relating to brain amyloid burden by SOMAscan assay

Plasma proteins have been widely studied as candidate biomarkers to predict brain amyloid deposition to increase recruitment efficiency in secondary prevention clinical trials for Alzheimer's disease. Most such biomarker studies are targeted to specific proteins or are biased toward high abunda...

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Autores: Shi, Liu|||0000-0003-1752-0419, Westwood, Sarah|||0000-0003-0506-7813, Baird, Alison L., Winchester, Laura|||0000-0003-3826-7694, Dobricic, Valerija|||0000-0001-8559-1097, Kilpert, Fabian, Hong, Shengjun, Franke, Andre|||0000-0003-1530-5811, Hye, Abdul|||0000-0003-2237-4823, Ashton, Nicholas J.|||0000-0002-3579-8804, Morgan, Angharad R., Bos, Isabelle|||0000-0001-9648-6428, Vos, Stephanie J.B.|||0000-0002-2045-9818, Buckley, Noel J.|||0000-0003-1152-0653, ten Kate, Mara|||0000-0002-8290-8543, Scheltens, Philip|||0000-0002-1046-6408, Vandenberghe, Rik|||0000-0001-6237-2502, Gabel, Silvy, Meersmans, Karen, Engelborghs, Sebastiaan|||0000-0003-0304-9785, De Roeck, Ellen, Sleegers, Kristel|||0000-0002-0283-2332, Frisoni, Giovanni B.|||0000-0002-6419-1753, Blin, Olivier, Richardson, Jill|||0000-0001-6564-3187, Bordet, Régis|||0000-0003-3916-6422, Molinuevo, José Luis|||0000-0003-0485-6001, Rami Gonzalez, Lorena|||0000-0002-7411-1921, Wallin, Anders|||0000-0001-9506-0513, Kettunen, Petronella|||0000-0002-2510-3423, Tsolaki, Magda|||0000-0002-2072-8010, Verhey, Frans, Lleó, Alberto|||0000-0002-2568-5478, Alcolea, Daniel|||0000-0002-3819-3245, Popp, Julius|||0000-0002-0068-0312, Peyratout, Gwendoline, Martinez-Lage, Pablo|||0000-0001-5404-9967, Tainta, Mikel|||0000-0003-0624-1211, Johannsen, Peter, Teunissen, Charlotte E.|||0000-0002-4061-0837, Freund-Levi, Yvonne|||0000-0001-6863-6679, Froelich, Lutz|||0000-0003-1494-0813, Legido-Quigley, Cristina|||0000-0002-4018-214X, Barkhof, Frederik|||0000-0003-3543-3706, Blennow, Kaj|||0000-0002-1890-4193, Zetterberg, Henrik|||0000-0003-3930-4354, Baker, Susan, Morgan, B.Paul, Streffer, Johannes Rolf|||0000-0002-9387-5951, Visser, Pieter Jelle|||0000-0001-8008-9727, Bertram, Lars|||0000-0002-0108-124X, Lovestone, Simon|||0000-0003-0473-4565, Nevado-Holgado, Alejo|||0000-0001-9276-2720
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:286439
Acceso en línea:https://ddd.uab.cat/record/286439
https://dx.doi.org/urn:doi:10.1016/j.jalz.2019.06.4951
Access Level:acceso abierto
Palabra clave:Amyloid β
Causal relationship
Plasma proteomics
Replication
SOMAscan assay
Tau
Descripción
Sumario:Plasma proteins have been widely studied as candidate biomarkers to predict brain amyloid deposition to increase recruitment efficiency in secondary prevention clinical trials for Alzheimer's disease. Most such biomarker studies are targeted to specific proteins or are biased toward high abundant proteins. 4001 plasma proteins were measured in two groups of participants (discovery group = 516, replication group = 365) selected from the European Medical Information Framework for Alzheimer's disease Multimodal Biomarker Discovery study, all of whom had measures of amyloid. A panel of proteins (n = 44), along with age and apolipoprotein E (APOE) ε4, predicted brain amyloid deposition with good performance in both the discovery group (area under the curve = 0.78) and the replication group (area under the curve = 0.68). Furthermore, a causal relationship between amyloid and tau was confirmed by Mendelian randomization. The results suggest that high-dimensional plasma protein testing could be a useful and reproducible approach for measuring brain amyloid deposition.

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