Validation of Plasma Proteomic Biomarkers Relating to Brain Amyloid Burden in the EMIF-Alzheimer’s Disease Multimodal Biomarker Discovery Cohort
Sarah Westwood
(1)
,
Alison Baird
(1)
,
Sneha Anand
(1)
,
Alejo Nevado-Holgado
(1)
,
Andrey Kormilitzin
(1)
,
Liu Shi
(1)
,
Abdul Hye
(2)
,
Nicholas Ashton
(2, 3)
,
Angharad Morgan
(4)
,
Isabelle Bos
(5)
,
Stephanie J.B. Vos
(5)
,
Susan Baker
(6)
,
Noel Buckley
(1)
,
Mara ten Kate
(7)
,
Philip Scheltens
(7)
,
Charlotte Teunissen
(7)
,
Rik Vandenberghe
(8)
,
Silvy Gabel
(8, 9)
,
Karen Meersmans
(8, 9)
,
Sebastiaan Engelborghs
(10, 11)
,
Ellen de Roeck
(10, 11)
,
Kristel Sleegers
(11, 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)
,
Magda Tsolaki
(23)
,
Frans Verhey
(5)
,
Alberto Lléo
(24)
,
Isabel Sala
(24)
,
Julius Popp
(25)
,
Gwendoline Peyratout
(25)
,
Pablo Martinez-Lage
(25)
,
Mikel Tainta
(26)
,
Peter Johannsen
(27)
,
Yvonne Freund-Levi
(2, 28)
,
Lutz Frölich
(29)
,
Valerija Dobricic
(30)
,
Cristina Legido-Quigley
(2, 31)
,
Lars Bertram
(30, 32)
,
Frederik Barkhof
(7, 33)
,
Henrik Zetterberg
(3, 34, 35, 36)
,
B. Paul Morgan
(4)
,
Johannes Streffer
(11, 37)
,
Pieter Jelle Visser
(5, 7)
,
Simon Lovestone
(1)
1
University of Oxford
2 King‘s College London
3 GU - Göteborgs Universitet = University of Gothenburg
4 Cardiff University
5 Maastricht University [Maastricht]
6 Janssen Research & Development
7 VU University Medical Center [Amsterdam]
8 University Hospitals Leuven [Leuven]
9 KU Leuven - Catholic University of Leuven = Katholieke Universiteit Leuven
10 UA - University of Antwerp
11 VUB - Vrije Universiteit Brussel
12 VIB - Vlaams Instituut voor Biotechnologie [Ghent, Belgique]
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 Université de Lille
19 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
20 IDIBAPS - Institut d'Investigacions Biomèdiques August Pi i Sunyer
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 Center for Research and Advanced Therapies CITA-Alzheimer Foundation [San Sebastián]
27 Copenhagen University Hospital
28 Karolinska University Hospital [Stockholm]
29 Universität Heidelberg [Heidelberg] = Heidelberg University
30 Universität zu Lübeck = University of Lübeck [Lübeck]
31 Steno Diabetes Center
32 UiO - University of Oslo
33 Institutes of Neurology and Healthcare Engineering, UCL, London
34 Sahlgrenska University Hospital [Gothenburg]
35 UK DRI - UK Dementia Research Institute
36 UCL Queen Square Institute of Neurology
37 UCB Pharma S.A.[Braine-l'Alleud]
2 King‘s College London
3 GU - Göteborgs Universitet = University of Gothenburg
4 Cardiff University
5 Maastricht University [Maastricht]
6 Janssen Research & Development
7 VU University Medical Center [Amsterdam]
8 University Hospitals Leuven [Leuven]
9 KU Leuven - Catholic University of Leuven = Katholieke Universiteit Leuven
10 UA - University of Antwerp
11 VUB - Vrije Universiteit Brussel
12 VIB - Vlaams Instituut voor Biotechnologie [Ghent, Belgique]
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 Université de Lille
19 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
20 IDIBAPS - Institut d'Investigacions Biomèdiques August Pi i Sunyer
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 Center for Research and Advanced Therapies CITA-Alzheimer Foundation [San Sebastián]
27 Copenhagen University Hospital
28 Karolinska University Hospital [Stockholm]
29 Universität Heidelberg [Heidelberg] = Heidelberg University
30 Universität zu Lübeck = University of Lübeck [Lübeck]
31 Steno Diabetes Center
32 UiO - University of Oslo
33 Institutes of Neurology and Healthcare Engineering, UCL, London
34 Sahlgrenska University Hospital [Gothenburg]
35 UK DRI - UK Dementia Research Institute
36 UCL Queen Square Institute of Neurology
37 UCB Pharma S.A.[Braine-l'Alleud]
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
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
Pieter Jelle Visser
- Fonction : Auteur
- PersonId : 785160
- ORCID : 0000-0001-8008-9727
Résumé
We have previously investigated, discovered, and replicated plasma protein biomarkers for use to triage potential trials participants for PET or cerebrospinal fluid measures of Alzheimer's disease (AD) pathology. This study sought to undertake validation of these candidate plasma biomarkers in a large, multi-center sample collection. Targeted plasma analyses of 34 proteins with prior evidence for prediction of in vivo pathology were conducted in up to 1,000 samples from cognitively healthy elderly individuals, people with mild cognitive impairment, and in patients with AD-type dementia, selected from the EMIF-AD catalogue. Proteins were measured using Luminex xMAP, ELISA, and Meso Scale Discovery assays. Seven proteins replicated in their ability to predict in vivo amyloid pathology. These proteins form a biomarker panel that, along with age, could significantly discriminate between individuals with high and low amyloid pathology with an area under the curve of 0.74. The performance of this biomarker panel remained consistent when tested in apolipoprotein E ɛ4 non-carrier individuals only. This blood-based panel is biologically relevant, measurable using practical immunocapture arrays, and could significantly reduce the cost incurred to clinical trials through screen failure.