Discovery and validation of plasma proteomic biomarkers relating to brain amyloid burden by SOMAscan assay
Liu Shi
(1)
,
Sarah Westwood
(1)
,
Alison Baird
(1)
,
Laura Winchester
(1)
,
Valerija Dobricic
(2)
,
Fabian Kilpert
(2)
,
Shengjun Hong
(2)
,
Andre Franke
(3)
,
Abdul Hye
(4)
,
Nicholas Ashton
(4, 5)
,
Angharad Morgan
(6)
,
Isabelle Bos
(7)
,
Stephanie J.B. Vos
(8)
,
Noel Buckley
(1)
,
Mara Ten Kate
(8)
,
Philip Scheltens
(8)
,
Rik Vandenberghe
(9)
,
Silvy Gabel
(9, 10)
,
Karen Meersmans
(9, 10)
,
Sebastiaan Engelborghs
(11, 12)
,
Ellen de Roeck
(11, 12)
,
Kristel Sleegers
(12)
,
Giovanni Frisoni
(13, 14)
,
Olivier Blin
(15, 16)
,
Jill Richardson
(17)
,
Régis Bordet
(18, 19)
,
José Molinuevo
(20, 21)
,
Lorena Rami
(21)
,
Anders Wallin
(22)
,
Petronella Kettunen
(22, 1)
,
Magda Tsolaki
(23)
,
Frans Verhey
(7)
,
Alberto Lleó
(24)
,
Daniel Alcolea
(24)
,
Julius Popp
(25, 26)
,
Gwendoline Peyratout
(25)
,
Pablo Martinez-Lage
(27)
,
Mikel Tainta
(27)
,
Peter Johannsen
(28)
,
Charlotte Teunissen
(29, 30)
,
Yvonne Freund-Levi
(31, 32, 4)
,
Lutz Frölich
(33)
,
Cristina Legido-Quigley
(4)
,
Frederik Barkhof
(8, 34)
,
Kaj Blennow
(35, 5)
,
Henrik Zetterberg
(5, 35, 36)
,
Susan Baker
(37)
,
B. Paul Morgan
(6)
,
Johannes Streffer
(12)
,
Pieter Jelle Visser
(7, 8, 31)
,
Lars Bertram
(2, 38)
,
Simon Lovestone
(1)
,
Alejo Nevado-Holgado
(1)
1
University of Oxford
2 Universität zu Lübeck = University of Lübeck [Lübeck]
3 CAU - Christian-Albrechts-Universität zu Kiel = Christian-Albrechts University of Kiel = Université Christian-Albrechts de Kiel
4 King‘s College London
5 GU - Göteborgs Universitet = University of Gothenburg
6 Cardiff University
7 Maastricht University [Maastricht]
8 VU University Medical Center [Amsterdam]
9 University Hospitals Leuven [Leuven]
10 KU Leuven - Catholic University of Leuven = Katholieke Universiteit Leuven
11 VUB - Vrije Universiteit Brussel [Bruxelles]
12 UA - University of Antwerp
13 UNIGE - Université de Genève = University of Geneva
14 Istituto Centro San Giovanni di Dio Fatebenefratelli
15 INS - Institut de Neurosciences des Systèmes
16 APHM - Assistance Publique - Hôpitaux de Marseille
17 GSK - GlaxoSmithKline [Stevenage, UK]
18 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
19 Université de Lille
20 IDIBAPS - Hospital Clinic
21 UPF - Universitat Pompeu Fabra [Barcelona]
22 Sahlgrenska Academy at University of Gothenburg [Göteborg]
23 AHEPA University General Hospital [Thessaloniki]
24 Hospital de la Santa Creu i Sant Pau
25 CHUV - Centre Hospitalier Universitaire Vaudois = Lausanne University Hospital [Lausanne]
26 HUG - Geneva University Hospital
27 CITA-Alzheimer - Center for Research and Advanced Therapies = Centro de Investigación y Terapias Avanzadas
28 Copenhagen University Hospital
29 Amsterdam UMC - Amsterdam University Medical Centers
30 VU - Vrije Universiteit Amsterdam [Amsterdam]
31 Karolinska Institutet [Stockholm]
32 Örebro University
33 Universität Heidelberg [Heidelberg] = Heidelberg University
34 Institutes of Neurology and Healthcare Engineering, UCL, London
35 Sahlgrenska University Hospital [Gothenburg]
36 UCL Queen Square Institute of Neurology
37 Janssen Research & Development
38 UiO - University of Oslo
2 Universität zu Lübeck = University of Lübeck [Lübeck]
3 CAU - Christian-Albrechts-Universität zu Kiel = Christian-Albrechts University of Kiel = Université Christian-Albrechts de Kiel
4 King‘s College London
5 GU - Göteborgs Universitet = University of Gothenburg
6 Cardiff University
7 Maastricht University [Maastricht]
8 VU University Medical Center [Amsterdam]
9 University Hospitals Leuven [Leuven]
10 KU Leuven - Catholic University of Leuven = Katholieke Universiteit Leuven
11 VUB - Vrije Universiteit Brussel [Bruxelles]
12 UA - University of Antwerp
13 UNIGE - Université de Genève = University of Geneva
14 Istituto Centro San Giovanni di Dio Fatebenefratelli
15 INS - Institut de Neurosciences des Systèmes
16 APHM - Assistance Publique - Hôpitaux de Marseille
17 GSK - GlaxoSmithKline [Stevenage, UK]
18 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
19 Université de Lille
20 IDIBAPS - Hospital Clinic
21 UPF - Universitat Pompeu Fabra [Barcelona]
22 Sahlgrenska Academy at University of Gothenburg [Göteborg]
23 AHEPA University General Hospital [Thessaloniki]
24 Hospital de la Santa Creu i Sant Pau
25 CHUV - Centre Hospitalier Universitaire Vaudois = Lausanne University Hospital [Lausanne]
26 HUG - Geneva University Hospital
27 CITA-Alzheimer - Center for Research and Advanced Therapies = Centro de Investigación y Terapias Avanzadas
28 Copenhagen University Hospital
29 Amsterdam UMC - Amsterdam University Medical Centers
30 VU - Vrije Universiteit Amsterdam [Amsterdam]
31 Karolinska Institutet [Stockholm]
32 Örebro University
33 Universität Heidelberg [Heidelberg] = Heidelberg University
34 Institutes of Neurology and Healthcare Engineering, UCL, London
35 Sahlgrenska University Hospital [Gothenburg]
36 UCL Queen Square Institute of Neurology
37 Janssen Research & Development
38 UiO - University of Oslo
Nicholas Ashton
- Fonction : Auteur
- PersonId : 821859
- ORCID : 0000-0002-3579-8804
Giovanni Frisoni
- Fonction : Auteur
- PersonId : 768850
- ORCID : 0000-0001-7075-7082
Olivier Blin
- Fonction : Auteur
- PersonId : 780347
- ORCID : 0000-0003-0142-0931
Alberto Lleó
- Fonction : Auteur
- PersonId : 792181
- ORCID : 0000-0002-2568-5478
Daniel Alcolea
- Fonction : Auteur
- PersonId : 797376
- ORCID : 0000-0002-3819-3245
Yvonne Freund-Levi
- Fonction : Auteur
- PersonId : 801316
- ORCID : 0000-0001-6863-6679
Frederik Barkhof
- Fonction : Auteur
- PersonId : 772998
- ORCID : 0000-0003-3543-3706
- IdRef : 138520682
Kaj Blennow
- Fonction : Auteur
- PersonId : 763020
- ORCID : 0000-0002-1890-4193
Henrik Zetterberg
- Fonction : Auteur
- PersonId : 763019
- ORCID : 0000-0003-3930-4354
Pieter Jelle Visser
- Fonction : Auteur
- PersonId : 785160
- ORCID : 0000-0001-8008-9727
Résumé
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.