Replication study of plasma proteins relating to Alzheimer's pathology.


Journal

Alzheimer's & dementia : the journal of the Alzheimer's Association
ISSN: 1552-5279
Titre abrégé: Alzheimers Dement
Pays: United States
ID NLM: 101231978

Informations de publication

Date de publication:
09 2021
Historique:
revised: 26 11 2020
received: 24 07 2020
accepted: 05 02 2021
pubmed: 2 4 2021
medline: 31 12 2021
entrez: 1 4 2021
Statut: ppublish

Résumé

This study sought to discover and replicate plasma proteomic biomarkers relating to Alzheimer's disease (AD) including both the "ATN" (amyloid/tau/neurodegeneration) diagnostic framework and clinical diagnosis. Plasma proteins from 972 subjects (372 controls, 409 mild cognitive impairment [MCI], and 191 AD) were measured using both SOMAscan and targeted assays, including 4001 and 25 proteins, respectively. Protein co-expression network analysis of SOMAscan data revealed the relation between proteins and "N" varied across different neurodegeneration markers, indicating that the ATN variants are not interchangeable. Using hub proteins, age, and apolipoprotein E ε4 genotype discriminated AD from controls with an area under the curve (AUC) of 0.81 and MCI convertors from non-convertors with an AUC of 0.74. Targeted assays replicated the relation of four proteins with the ATN framework and clinical diagnosis. Our study suggests that blood proteins can predict the presence of AD pathology as measured in the ATN framework as well as clinical diagnosis.

Identifiants

pubmed: 33792144
doi: 10.1002/alz.12322
doi:

Substances chimiques

Amyloid beta-Peptides 0
Apolipoprotein E4 0
Biomarkers 0
Blood Proteins 0
tau Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1452-1464

Subventions

Organisme : Department of Health
Pays : United Kingdom

Informations de copyright

© 2021 the Alzheimer's Association.

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Auteurs

Liu Shi (L)

Department of Psychiatry, University of Oxford, Oxford, UK.

Laura M Winchester (LM)

Department of Psychiatry, University of Oxford, Oxford, UK.

Sarah Westwood (S)

Department of Psychiatry, University of Oxford, Oxford, UK.

Alison L Baird (AL)

Department of Psychiatry, University of Oxford, Oxford, UK.

Sneha N Anand (SN)

Department of Psychiatry, University of Oxford, Oxford, UK.

Noel J Buckley (NJ)

Department of Psychiatry, University of Oxford, Oxford, UK.

Abdul Hye (A)

Maurice Wohl Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, UK.

Nicholas J Ashton (NJ)

Maurice Wohl Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, UK.
Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.

Isabelle Bos (I)

Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Centrum Limburg, Maastricht University, Maastricht, the Netherlands.
Alzheimer Center, VU University Medical Center, Amsterdam, the Netherlands.

Stephanie J B Vos (SJB)

Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Centrum Limburg, Maastricht University, Maastricht, the Netherlands.

Mara Ten Kate (MT)

Alzheimer Center, VU University Medical Center, Amsterdam, the Netherlands.

Philip Scheltens (P)

Alzheimer Center, VU University Medical Center, Amsterdam, the Netherlands.

Charlotte E Teunissen (CE)

Neurochemistry lab, Department of Clinical Chemistry, Amsterdam University Medical Centers, Vrije Universiteit, Amsterdam Neuroscience, Amsterdam, the Netherlands.

Rik Vandenberghe (R)

University Hospital Leuven, Leuven, Belgium.

Silvy Gabel (S)

University Hospital Leuven, Leuven, Belgium.
Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven, Belgium.

Karen Meersmans (K)

University Hospital Leuven, Leuven, Belgium.
Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven, Belgium.

Sebastiaan Engelborghs (S)

Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
Department of Neurology, UZ Brussel and Center for Neurociences (C4N), Vrije Universiteit Brussel, Brussels, Belgium.

Ellen E De Roeck (EE)

Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium.

Kristel Sleegers (K)

Complex Genetics Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium.
Institute Born-Bunge, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.

Giovanni B Frisoni (GB)

University of Geneva, Geneva, Switzerland.
IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.

Olivier Blin (O)

AIX marseille university, INS, Ap-hm, Marseille, France.

Jill C Richardson (JC)

Neurosciences Therapeutic Area, GlaxoSmithKline R&D, Stevenage, UK.

Régis Bordet (R)

Inserm, University of Lille, CHU Lille, Lille, France.

José L Molinuevo (JL)

Alzheimer's Disease and Other Cognitive Disorders Unit, Hopsital Clínic-IDIBAPS, Barcelona, Spain.
Barcelona Beta Brain Research Center, Unversitat Pompeu Fabra, Barcelona, Spain.

Lorena Rami (L)

Barcelona Beta Brain Research Center, Unversitat Pompeu Fabra, Barcelona, Spain.

Anders Wallin (A)

Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.

Petronella Kettunen (P)

Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.

Magda Tsolaki (M)

1st Department of Neurology, AHEPA University Hospital, Makedonia, Thessaloniki, Greece.

Frans Verhey (F)

Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Centrum Limburg, Maastricht University, Maastricht, the Netherlands.

Alberto Lléo (A)

Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.

Isabel Sala (I)

Department of Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.

Julius Popp (J)

University Hospital of Lausanne, Lausanne, Switzerland.
Geriatric Psychiatry, Department of Mental Health and Psychiatry, Geneva University Hospitals, Geneva, Switzerland.

Gwendoline Peyratout (G)

University Hospital of Lausanne, Lausanne, Switzerland.

Pablo Martinez-Lage (P)

CITA-Alzheimer Foundation, San Sebastian, Spain.

Mikel Tainta (M)

CITA-Alzheimer Foundation, San Sebastian, Spain.

Peter Johannsen (P)

Danish Dementia Research Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Yvonne Freund-Levi (Y)

Maurice Wohl Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, UK.
Karolinska Institutet Center for Alzheimer Research, Division of Clinical Geriatrics, School of Medical Sciences Örebro University and Department of Neurobiology, Caring Sciences and Society (NVS), Stockholm, Sweden.

Lutz Frölich (L)

Department of Geriatric Psychiatry, Zentralinstitut für Seelische Gesundheit, University of Heidelberg, Mannheim, Germany.

Valerija Dobricic (V)

Lübeck Interdisciplinary Platform for Genome Analytics, Institutes of Neurogenetics and Cardiogenetics, University of Lübeck, Lübeck, Germany.

Cristina Legido-Quigley (C)

Kings College London, London, UK.
The Systems Medicine Group, Steno Diabetes Center, Gentofte, Denmark.

Frederik Barkhof (F)

Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherland.
UCL Institutes of Neurology and Healthcare Engineering, London, UK.

Ulf Andreasson (U)

Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.

Kaj Blennow (K)

Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.

Henrik Zetterberg (H)

Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
UK Dementia Research Institute at UCL, London, UK.
Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.

Johannes Streffer (J)

Complex Genetics Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium.
UCB, Braine-l'Alleud, Belgium, formerly Janssen R&D, LLC Beerse, Beerse, Belgium.

Christina M Lill (CM)

Section for Translational Surgical Oncology and Biobanking, Department of Surgery, University of Lübeck and University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.
Ageing Epidemiology Research Unit, School of Public Health, Imperial College, London, UK.

Lars Bertram (L)

Lübeck Interdisciplinary Platform for Genome Analytics, Institutes of Neurogenetics and Cardiogenetics, University of Lübeck, Lübeck, Germany.
Department of Psychology, University of Oslo, Oslo, Norway.

Pieter Jelle Visser (PJ)

Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Centrum Limburg, Maastricht University, Maastricht, the Netherlands.
Alzheimer Center, VU University Medical Center, Amsterdam, the Netherlands.

Hartmuth C Kolb (HC)

Janssen R&D, Beerse, UK.

Vaibhav A Narayan (VA)

Janssen R&D, Beerse, UK.

Simon Lovestone (S)

Department of Psychiatry, University of Oxford, Oxford, UK.
Janssen R&D, Beerse, UK.

Alejo J Nevado-Holgado (AJ)

Department of Psychiatry, University of Oxford, Oxford, UK.

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