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

Liu Shi, Sarah Westwood, Alison L. Baird, Laura Winchester, Valerija Dobricic, Fabian Kilpert, Shengjun Hong, Andre Franke, Abdul Hye, Nicholas J. Ashton, Angharad R. Morgan, Isabelle Bos, Stephanie J. B. Vos, Noel J. Buckley, Mara ten Kate, Philip Scheltens, Rik Vandenberghe, Silvy Gabel, Karen Meersmans, Sebastiaan EngelborghsEllen E. de Roeck, Kristel Sleegers, Giovanni B. Frisoni, Olivier Blin, Jill C. Richardson, R. gis Bordet, José L. Molinuevo, Lorena Rami, Anders Wallin, Petronella Kettunen, Magda Tsolaki, Frans Verhey, Alberto Lleó, Daniel Alcolea, Julius Popp, Gwendoline Peyratout, Pablo Martinez-Lage, Mikel Tainta, Peter Johannsen, Charlotte E. Teunissen, Yvonne Freund-Levi, Lutz Frölich, Cristina Legido-Quigley, Frederik Barkhof, Kaj Blennow, Henrik Zetterberg, Susan Baker, B. Paul Morgan, Johannes Streffer, Pieter Jelle Visser, Lars Bertram, Simon Lovestone, Alejo J. Nevado-Holgado

Research output: Contribution to journalArticleAcademicpeer-review

39 Citations (Scopus)


Introduction: 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. Methods: 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. Results: 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. Discussion: The results suggest that high-dimensional plasma protein testing could be a useful and reproducible approach for measuring brain amyloid deposition.
Original languageEnglish
Pages (from-to)1478-1488
JournalAlzheimer's and Dementia
Issue number11
Publication statusPublished - Nov 2019


  • Amyloid β
  • Causal relationship
  • Plasma proteomics
  • Replication
  • SOMAscan assay
  • Tau

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