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Plasma Proteomic Biomarkers Relating to Alzheimer’s Disease: A Meta-Analysis Based on Our Own Studies

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  • Liu Shi
  • Noel J. Buckley
  • Isabelle Bos
  • Sebastiaan Engelborghs
  • Kristel Sleegers
  • Giovanni B. Frisoni
  • Anders Wallin
  • Alberto Lléo
  • Julius Popp
  • Pablo Martinez-Lage
  • Cristina Legido-Quigley
  • Frederik Barkhof
  • Henrik Zetterberg
  • Pieter Jelle Visser
  • Lars Bertram
  • Simon Lovestone
  • Alejo J. Nevado-Holgado
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Background and Objective: Plasma biomarkers for the diagnosis and stratification of Alzheimer’s disease (AD) are intensively sought. However, no plasma markers are well established so far for AD diagnosis. Our group has identified and validated various blood-based proteomic biomarkers relating to AD pathology in multiple cohorts. The study aims to conduct a meta-analysis based on our own studies to systematically assess the diagnostic performance of our previously identified blood biomarkers. Methods: To do this, we included seven studies that our group has conducted during the last decade. These studies used either Luminex xMAP or ELISA to measure proteomic biomarkers. As proteins measured in these studies differed, we selected protein based on the criteria that it must be measured in at least four studies. We then examined biomarker performance using random-effect meta-analyses based on the mean difference between biomarker concentrations in AD and controls (CTL), AD and mild cognitive impairment (MCI), MCI, and CTL as well as MCI converted to dementia (MCIc) and non-converted (MCInc) individuals. Results: An overall of 2,879 subjects were retrieved for meta-analysis including 1,053 CTL, 895 MCI, 882 AD, and 49 frontotemporal dementia (FTD) patients. Six proteins were measured in at least four studies and were chosen for meta-analyses for AD diagnosis. Of them, three proteins had significant difference between AD and controls, among which alpha-2-macroglobulin (A2M) and ficolin-2 (FCN2) increased in AD while fibrinogen gamma chain (FGG) decreased in AD compared to CTL. Furthermore, FGG significantly increased in FTD compared to AD. None of the proteins passed the significance between AD and MCI, or MCI and CTL, or MCIc and MCInc, although complement component 4 (CC4) tended to increase in MCIc individuals compared to MCInc. Conclusions: The results suggest that A2M, FCN2, and FGG are promising biomarkers to discriminate AD patients from controls, which are worthy of further validation.

Original languageEnglish
Article number712545
JournalFrontiers in Aging Neuroscience
Volume13
ISSN1663-4365
DOIs
Publication statusPublished - 21 Jul 2021

Bibliographical note

Funding Information:
We acknowledge the contribution of the personnel of the Genomic Service Facility at the VIB-U Antwerp Center for Molecular Neurology. Funding. This research was conducted as part of the EMIF-AD project which has received support from the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement no. 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 San Sebastian GAP study was partially funded by the Department of Health of the Basque Government (allocation 17.0.1.08.12.0000.2.454.01.41142.001.H). The research at VIB-CMN was funded in part by the University of Antwerp Research Fund.

Funding Information:
This research was conducted as part of the EMIF-AD project which has received support from the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement no. 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 San Sebastian GAP study was partially funded by the Department of Health of the Basque Government (allocation 17.0.1.08.12.0000.2.454.01.41142.001.H). The research at VIB-CMN was funded in part by the University of Antwerp Research Fund.

Publisher Copyright:
© Copyright © 2021 Shi, Buckley, Bos, Engelborghs, Sleegers, Frisoni, Wallin, Lléo, Popp, Martinez-Lage, Legido-Quigley, Barkhof, Zetterberg, Visser, Bertram, Lovestone and Nevado-Holgado.

    Research areas

  • Alzheimer’s disease (AD), blood biomarkers, diagnosis, meta-analysis, proteomic

ID: 69206117