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 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 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

doi:10.1016/j.jalz.2019.06.4951

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, Régis 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

^*Korrespondierende/r Autor/-in für diese Arbeit

53 Zitate (Scopus)

Abstract

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.

Originalsprache	Englisch
Zeitschrift	Alzheimer's and Dementia
Jahrgang	15
Ausgabenummer	11
Seiten (von - bis)	1478-1488
Seitenumfang	11
ISSN	1552-5260
DOIs	https://doi.org/10.1016/j.jalz.2019.06.4951
Publikationsstatus	Veröffentlicht - 11.2019

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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 Program (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). R.V. is a senior clinical investigator of the Flemish Research Foundation (FWO). J.S. is currently an employee of UCB, Braine-l’Alleud, Belgium. 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). The authors 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. F.B. is supported by the NIHR biomedical research centre at UCLH. L.S. is funded by DPUK through MRC (grant no. MR/L023784/2 ) and the UK Medical Research Council Award to the University of Oxford (grant no. MC_PC_17215 ).

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10.1016/j.jalz.2019.06.4951

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Shi, L., Westwood, S., Baird, A. L., Winchester, L., Dobricic, V., Kilpert, F., Hong, S., Franke, A., Hye, A., Ashton, N. J., Morgan, A. R., Bos, I., Vos, S. J. B., Buckley, N. J., Kate, M. T., Scheltens, P., Vandenberghe, R., Gabel, S., Meersmans, K., ... Nevado-Holgado, A. J. (2019). Discovery and validation of plasma proteomic biomarkers relating to brain amyloid burden by SOMAscan assay. Alzheimer's and Dementia, 15(11), 1478-1488. https://doi.org/10.1016/j.jalz.2019.06.4951

@article{b1e70f88da63465aac31fcd194e3bfb6,

title = "Discovery and validation of plasma proteomic biomarkers relating to brain amyloid burden by SOMAscan assay",

abstract = "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.",

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

note = "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 Program (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). R.V. is a senior clinical investigator of the Flemish Research Foundation (FWO). J.S. is currently an employee of UCB, Braine-l{\textquoteright}Alleud, Belgium. 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). The authors 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. F.B. is supported by the NIHR biomedical research centre at UCLH. L.S. is funded by DPUK through MRC (grant no. MR/L023784/2 ) and the UK Medical Research Council Award to the University of Oxford (grant no. MC\_PC\_17215 ). Publisher Copyright: {\textcopyright} 2019 The Authors Copyright: Copyright 2019 Elsevier B.V., All rights reserved.",

year = "2019",

month = nov,

doi = "10.1016/j.jalz.2019.06.4951",

language = "English",

volume = "15",

pages = "1478--1488",

journal = "Alzheimer's and Dementia",

issn = "1552-5260",

publisher = "John Wiley and Sons Inc",

number = "11",

}

Shi, L, Westwood, S, Baird, AL, Winchester, L, Dobricic, V, Kilpert, F, Hong, S, Franke, A, Hye, A, Ashton, NJ, Morgan, AR, Bos, I, Vos, SJB, Buckley, NJ, Kate, MT, Scheltens, P, Vandenberghe, R, Gabel, S, Meersmans, K, Engelborghs, S, De Roeck, EE, Sleegers, K, Frisoni, GB, Blin, O, Richardson, JC, Bordet, R, Molinuevo, JL, Rami, L, Wallin, A, Kettunen, P, Tsolaki, M, Verhey, F, Lleó, A, Alcolea, D, Popp, J, Peyratout, G, Martinez-Lage, P, Tainta, M, Johannsen, P, Teunissen, CE, Freund-Levi, Y, Frölich, L, Legido-Quigley, C, Barkhof, F, Blennow, K, Zetterberg, H, Baker, S, Morgan, BP, Streffer, J, Visser, PJ, Bertram, L, Lovestone, S & Nevado-Holgado, AJ 2019, 'Discovery and validation of plasma proteomic biomarkers relating to brain amyloid burden by SOMAscan assay', Alzheimer's and Dementia, Jg. 15, Nr. 11, S. 1478-1488. https://doi.org/10.1016/j.jalz.2019.06.4951

TY - JOUR

T1 - Discovery and validation of plasma proteomic biomarkers relating to brain amyloid burden by SOMAscan assay

AU - Shi, Liu

AU - Westwood, Sarah

AU - Baird, Alison L.

AU - Winchester, Laura

AU - Dobricic, Valerija

AU - Kilpert, Fabian

AU - Hong, Shengjun

AU - Franke, Andre

AU - Hye, Abdul

AU - Ashton, Nicholas J.

AU - Morgan, Angharad R.

AU - Bos, Isabelle

AU - Vos, Stephanie J.B.

AU - Buckley, Noel J.

AU - Kate, Mara ten

AU - Scheltens, Philip

AU - Vandenberghe, Rik

AU - Gabel, Silvy

AU - Meersmans, Karen

AU - Engelborghs, Sebastiaan

AU - De Roeck, Ellen E.

AU - Sleegers, Kristel

AU - Frisoni, Giovanni B.

AU - Blin, Olivier

AU - Richardson, Jill C.

AU - Bordet, Régis

AU - Molinuevo, José L.

AU - Rami, Lorena

AU - Wallin, Anders

AU - Kettunen, Petronella

AU - Tsolaki, Magda

AU - Verhey, Frans

AU - Lleó, Alberto

AU - Alcolea, Daniel

AU - Popp, Julius

AU - Peyratout, Gwendoline

AU - Martinez-Lage, Pablo

AU - Tainta, Mikel

AU - Johannsen, Peter

AU - Teunissen, Charlotte E.

AU - Freund-Levi, Yvonne

AU - Frölich, Lutz

AU - Legido-Quigley, Cristina

AU - Barkhof, Frederik

AU - Blennow, Kaj

AU - Zetterberg, Henrik

AU - Baker, Susan

AU - Morgan, B. Paul

AU - Streffer, Johannes

AU - Visser, Pieter Jelle

AU - Bertram, Lars

AU - Lovestone, Simon

AU - Nevado-Holgado, Alejo J.

N1 - 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 Program (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). R.V. is a senior clinical investigator of the Flemish Research Foundation (FWO). J.S. is currently an employee of UCB, Braine-l’Alleud, Belgium. 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). The authors 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. F.B. is supported by the NIHR biomedical research centre at UCLH. L.S. is funded by DPUK through MRC (grant no. MR/L023784/2 ) and the UK Medical Research Council Award to the University of Oxford (grant no. MC_PC_17215 ). Publisher Copyright: © 2019 The Authors Copyright: Copyright 2019 Elsevier B.V., All rights reserved.

PY - 2019/11

Y1 - 2019/11

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85071719989

U2 - 10.1016/j.jalz.2019.06.4951

DO - 10.1016/j.jalz.2019.06.4951

M3 - Journal articles

C2 - 31495601

AN - SCOPUS:85071719989

SN - 1552-5260

VL - 15

SP - 1478

EP - 1488

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - 11

ER -

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

Abstract

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