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Rigshospitalet - a part of Copenhagen University Hospital
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Replication study of plasma proteins relating to Alzheimer's pathology

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  • Liu Shi
  • Laura M. Winchester
  • Sarah Westwood
  • Alison L. Baird
  • Sneha N. Anand
  • Noel J. Buckley
  • Abdul Hye
  • Nicholas J. Ashton
  • Isabelle Bos
  • Stephanie J.B. Vos
  • Mara ten Kate
  • Philip Scheltens
  • Charlotte E. Teunissen
  • Rik Vandenberghe
  • Silvy Gabel
  • Karen Meersmans
  • Sebastiaan Engelborghs
  • Ellen E. De Roeck
  • Kristel Sleegers
  • Giovanni B. Frisoni
  • Olivier Blin
  • Jill C. Richardson
  • Régis Bordet
  • José L. Molinuevo
  • Lorena Rami
  • Anders Wallin
  • Petronella Kettunen
  • Magda Tsolaki
  • Frans Verhey
  • Alberto Lléo
  • Isabel Sala
  • Julius Popp
  • Gwendoline Peyratout
  • Pablo Martinez-Lage
  • Mikel Tainta
  • Peter Johannsen
  • Yvonne Freund-Levi
  • Lutz Frölich
  • Valerija Dobricic
  • Cristina Legido-Quigley
  • Frederik Barkhof
  • Ulf Andreasson
  • Kaj Blennow
  • Henrik Zetterberg
  • Johannes Streffer
  • Christina M. Lill
  • Lars Bertram
  • Pieter Jelle Visser
  • Hartmuth C. Kolb
  • Vaibhav A. Narayan
  • Simon Lovestone
  • Alejo J. Nevado-Holgado
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Introduction: This study sought to discover and replicate plasma proteomic biomarkers relating to Alzheimer's disease (AD) including both the “ATN” (amyloid/tau/neurodegeneration) diagnostic framework and clinical diagnosis. Methods: Plasma proteins from 972 subjects (372 controls, 409 mild cognitive impairment [MCI], and 191 AD) were measured using both SOMAscan and targeted assays, including 4001 and 25 proteins, respectively. Results: Protein co-expression network analysis of SOMAscan data revealed the relation between proteins and “N” varied across different neurodegeneration markers, indicating that the ATN variants are not interchangeable. Using hub proteins, age, and apolipoprotein E ε4 genotype discriminated AD from controls with an area under the curve (AUC) of 0.81 and MCI convertors from non-convertors with an AUC of 0.74. Targeted assays replicated the relation of four proteins with the ATN framework and clinical diagnosis. Discussion: Our study suggests that blood proteins can predict the presence of AD pathology as measured in the ATN framework as well as clinical diagnosis.

Original languageEnglish
JournalAlzheimer's and Dementia
Volume17
Issue number9
Pages (from-to)1452-1464
Number of pages13
ISSN1552-5260
DOIs
Publication statusPublished - Sep 2021

Bibliographical note

Funding Information:
This research was conducted as part of the EMIF-AD MBD project, which has received support from the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement n? 115372, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies? in-kind contribution. The DESCRIPA study was funded by the European Commission within the 5th framework program (QLRT-2001-2455). The EDAR study was funded by the European Commission within the 5th framework program (contract # 37670). The Leuven cohort was funded by the Stichting voor Alzheimer Onderzoek (grant numbers #11020, #13007, and #15005). RV is a senior clinical investigator of the Flemish Research Foundation (FWO). The San Sebastian GAP study is partially funded by the Department of Health of the Basque Government (allocation 17.0.1.08.12.0000.2.454.01.41142.001.H). We acknowledge the contribution of the personnel of the Genomic Service Facility at the VIB-U Antwerp Center for Molecular Neurology. The research at VIB-CMN is funded in part by the University of Antwerp Research Fund. HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018-02532); the European Research Council (#681712); Swedish State Support for Clinical Research (#ALFGBG-720931); the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862); and the UK Dementia Research Institute at UCL. FB is supported by the NIHR biomedical research center at UCLH.

Publisher Copyright:
© 2021 the Alzheimer's Association

    Research areas

  • Alzheimer's disease, ATN framework, biomarker, dementia, network analysis, plasma proteomics, replication

ID: 69207154