Inflammatory biomarkers in Alzheimer's disease plasma
Angharad Morgan
(1)
,
Samuel Touchard
(1)
,
Claire Leckey
(1)
,
Caroline O'Hagan
(1)
,
Alejo Nevado‐holgado
(2)
,
Frederik Barkhof
(3, 4)
,
Lars Bertram
(5)
,
Olivier Blin
(6, 7)
,
Isabelle Bos
(8)
,
Valerija Dobricic
(9)
,
Sebastiaan Engelborghs
(10)
,
Giovanni Frisoni
(11, 12)
,
Lutz Frölich
(13)
,
Silvey Gabel
(14)
,
Peter Johannsen
(15)
,
Petronella Kettunen
(16)
,
Iwona Kłoszewska
(17)
,
Cristina Legido‐quigley
(4, 18)
,
Alberto Lleó
(19)
,
Pablo Martinez‐lage
(20)
,
Patrizia Mecocci
(21)
,
Karen Meersmans
(14)
,
José Luis Molinuevo
(22)
,
Gwendoline Peyratout
(23)
,
Julius Popp
(24, 11)
,
Jill Richardson
(25)
,
Isabel Sala
(19)
,
Philip Scheltens
(26, 27)
,
Johannes Streffer
(28)
,
Hikka Soininen
(29)
,
Mikel Tainta‐cuezva
(20)
,
Charlotte Teunissen
(30)
,
Magda Tsolaki
(31)
,
Rik Vandenberghe
(26)
,
Pieter Jelle Visser
(8)
,
Stephanie Vos
(8)
,
Lars‐olof Wahlund
(15)
,
Anders Wallin
(32)
,
Sarah Westwood
(2)
,
Henrik Zetterberg
(33, 16, 34)
,
Simon Lovestone
(2)
,
B. Paul Morgan
(1)
1
Cardiff University
2 University of Oxford
3 VU University Medical Center [Amsterdam]
4 UCL - University College of London [London]
5 MPIMG - Max Planck Institute for Molecular Genetics
6 INS - Institut de Neurosciences des Systèmes
7 APHM - Assistance Publique - Hôpitaux de Marseille
8 Maastricht University [Maastricht]
9 Universität zu Lübeck = University of Lübeck [Lübeck]
10 Institute Born-Bunge [Antwerp, Belgium]
11 UNIGE - Université de Genève = University of Geneva
12 Istituto Centro San Giovanni di Dio Fatebenefratelli
13 Universität Heidelberg [Heidelberg] = Heidelberg University
14 KU Leuven - Catholic University of Leuven = Katholieke Universiteit Leuven
15 Karolinska Institutet [Stockholm]
16 GU - Göteborgs Universitet = University of Gothenburg
17 MUL - Medical University of Łódź
18 Imperial College London
19 Hospital de la Santa Creu i Sant Pau
20 Center for Research and Advanced Therapies CITA-Alzheimer Foundation [San Sebastián]
21 UNIPG - Università degli Studi di Perugia = University of Perugia
22 UPF - Universitat Pompeu Fabra [Barcelona]
23 CHUV - Centre Hospitalier Universitaire Vaudois = Lausanne University Hospital [Lausanne]
24 HUG - Hôpitaux Universitaires de Genève
25 GSK - GlaxoSmithKline [Stevenage, UK]
26 Amsterdam UMC - Amsterdam University Medical Center
27 VU - Vrije Universiteit Amsterdam [Amsterdam]
28 UA - University of Antwerp
29 University of Eastern Finland
30 University Hospitals Leuven [Leuven]
31 AHEPA University General Hospital [Thessaloniki]
32 Sahlgrenska Academy at University of Gothenburg [Göteborg]
33 Sahlgrenska University Hospital [Gothenburg]
34 UCL Queen Square Institute of Neurology
2 University of Oxford
3 VU University Medical Center [Amsterdam]
4 UCL - University College of London [London]
5 MPIMG - Max Planck Institute for Molecular Genetics
6 INS - Institut de Neurosciences des Systèmes
7 APHM - Assistance Publique - Hôpitaux de Marseille
8 Maastricht University [Maastricht]
9 Universität zu Lübeck = University of Lübeck [Lübeck]
10 Institute Born-Bunge [Antwerp, Belgium]
11 UNIGE - Université de Genève = University of Geneva
12 Istituto Centro San Giovanni di Dio Fatebenefratelli
13 Universität Heidelberg [Heidelberg] = Heidelberg University
14 KU Leuven - Catholic University of Leuven = Katholieke Universiteit Leuven
15 Karolinska Institutet [Stockholm]
16 GU - Göteborgs Universitet = University of Gothenburg
17 MUL - Medical University of Łódź
18 Imperial College London
19 Hospital de la Santa Creu i Sant Pau
20 Center for Research and Advanced Therapies CITA-Alzheimer Foundation [San Sebastián]
21 UNIPG - Università degli Studi di Perugia = University of Perugia
22 UPF - Universitat Pompeu Fabra [Barcelona]
23 CHUV - Centre Hospitalier Universitaire Vaudois = Lausanne University Hospital [Lausanne]
24 HUG - Hôpitaux Universitaires de Genève
25 GSK - GlaxoSmithKline [Stevenage, UK]
26 Amsterdam UMC - Amsterdam University Medical Center
27 VU - Vrije Universiteit Amsterdam [Amsterdam]
28 UA - University of Antwerp
29 University of Eastern Finland
30 University Hospitals Leuven [Leuven]
31 AHEPA University General Hospital [Thessaloniki]
32 Sahlgrenska Academy at University of Gothenburg [Göteborg]
33 Sahlgrenska University Hospital [Gothenburg]
34 UCL Queen Square Institute of Neurology
Frederik Barkhof
- Fonction : Auteur
- PersonId : 772998
- ORCID : 0000-0003-3543-3706
- IdRef : 138520682
Olivier Blin
- Fonction : Auteur
- PersonId : 780347
- ORCID : 0000-0003-0142-0931
Giovanni Frisoni
- Fonction : Auteur
- PersonId : 768850
- ORCID : 0000-0001-7075-7082
Alberto Lleó
- Fonction : Auteur
- PersonId : 792181
- ORCID : 0000-0002-2568-5478
Pieter Jelle Visser
- Fonction : Auteur
- PersonId : 785160
- ORCID : 0000-0001-8008-9727
Henrik Zetterberg
- Fonction : Auteur
- PersonId : 763019
- ORCID : 0000-0003-3930-4354
Résumé
Introduction: Plasma biomarkers for Alzheimer's disease (AD) diagnosis/stratification are a "Holy Grail" of AD research and intensively sought; however, there are no well-established plasma markers.
Methods: A hypothesis-led plasma biomarker search was conducted in the context of international multicenter studies. The discovery phase measured 53 inflammatory proteins in elderly control (CTL; 259), mild cognitive impairment (MCI; 199), and AD (262) subjects from AddNeuroMed.
Results: Ten analytes showed significant intergroup differences. Logistic regression identified five (FB, FH, sCR1, MCP-1, eotaxin-1) that, age/APOε4 adjusted, optimally differentiated AD and CTL (AUC: 0.79), and three (sCR1, MCP-1, eotaxin-1) that optimally differentiated AD and MCI (AUC: 0.74). These models replicated in an independent cohort (EMIF; AUC 0.81 and 0.67). Two analytes (FB, FH) plus age predicted MCI progression to AD (AUC: 0.71).
Discussion: Plasma markers of inflammation and complement dysregulation support diagnosis and outcome prediction in AD and MCI. Further replication is needed before clinical translation.