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, Regis Bordet, Jose L. Molinuevo, Lorena Rami, Anders Wallin, Petronella Kettunen, Magda Tsolaki, Frans Verhey, Alberto Lleo, Daniel Alcolea, Julius Popp, Gwendoline Peyratout, Pablo Martinez-Lage, Mikel Tainta, Peter Johannsen, Charlotte E. Teunissen, Yvonne Freund-Levi, Lutz Froelich, 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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

30 Citations (Web of Science)


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) e4, 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. (C) 2019 The Authors. Published by Elsevier Inc.

Original languageEnglish
Pages (from-to)1478-1488
Number of pages11
JournalAlzheimer's & Dementia
Issue number11
Publication statusPublished - Nov 2019


  • Amyloid beta
  • SOMAscan assay
  • Plasma proteomics
  • Replication
  • Causal relationship
  • Tau
  • TAU
  • DRUG
  • AGE

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