Discovery and validation of plasma proteomic biomarkers relating to brain amyloid burden by SOMAscan assay
Por:
Shi, L, Westwood, S, Baird, AL, Winchester, L, Dobricic, V, Kilpert, F, Hong, SJ, Franke, A, Hye, A, Ashton, NJ, Morgan, AR, Bos, I, Vos, SJB, Buckley, NJ, ten Kate, M, 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, Lleo, A, Alcolea, D, Popp, J, Peyratout, G, Martinez-Lage, P, Tainta, M, Johannsen, P, Teunissen, CE, Freund-Levi, Y, Frolich, 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
Publicada:
1 nov 2019
Resumen:
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) e4, 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. (C) 2019 The Authors. Published by Elsevier Inc.
Filiaciones:
Shi, L:
Univ Oxford, Dept Psychiat, Oxford, England
Westwood, S:
Univ Oxford, Dept Psychiat, Oxford, England
Baird, AL:
Univ Oxford, Dept Psychiat, Oxford, England
Winchester, L:
Univ Oxford, Dept Psychiat, Oxford, England
Dobricic, V:
Univ Lubeck, Inst Neurogenet, Lubeck Interdisciplinary Platform Genome Analyt L, Lubeck, Germany
Univ Lubeck, Inst Cardiogenet, Lubeck Interdisciplinary Platform Genome Analyt L, Lubeck, Germany
Kilpert, F:
Univ Lubeck, Inst Neurogenet, Lubeck Interdisciplinary Platform Genome Analyt L, Lubeck, Germany
Univ Lubeck, Inst Cardiogenet, Lubeck Interdisciplinary Platform Genome Analyt L, Lubeck, Germany
Hong, SJ:
Univ Lubeck, Inst Neurogenet, Lubeck Interdisciplinary Platform Genome Analyt L, Lubeck, Germany
Univ Lubeck, Inst Cardiogenet, Lubeck Interdisciplinary Platform Genome Analyt L, Lubeck, Germany
Franke, A:
Christian Albrechts Univ Kiel, Inst Clin Mol Biol, Kiel, Germany
Hye, A:
Kings Coll London, Inst Psychiat Psychol & Neurosci, Maurice Wohl Clin Neurosci, London, England
Ashton, NJ:
Kings Coll London, Inst Psychiat Psychol & Neurosci, Maurice Wohl Clin Neurosci, London, England
Univ Gothenburg, Dept Psychiat & Neurochem, Molndal, Sweden
Univ Gothenburg, Wallenberg Ctr Mol & Translat Med, Gothenburg, Sweden
South London & Maudsley NHS Fdn, NIHR Biomed Res Ctr Mental Hlth, London, England
South London & Maudsley NHS Fdn, Biomed Res Unit Dementia, London, England
Morgan, AR:
Cardiff Univ, Dementia Res Inst Cardiff, Cardiff, S Glam, Wales
Bos, I:
Maastricht Univ, Alzheimer Ctr Limburg, Sch Mental Hlth & Neurosci, Dept Psychiat & Neuropsychol, Maastricht, Netherlands
Vos, SJB:
Vrije Univ Amsterdam Med Ctr, Alzheimer Ctr, Amsterdam, Netherlands
Buckley, NJ:
Univ Oxford, Dept Psychiat, Oxford, England
ten Kate, M:
Vrije Univ Amsterdam Med Ctr, Alzheimer Ctr, Amsterdam, Netherlands
Scheltens, P:
Vrije Univ Amsterdam Med Ctr, Alzheimer Ctr, Amsterdam, Netherlands
Vandenberghe, R:
Univ Hosp Leuven, Leuven, Belgium
Gabel, S:
Univ Hosp Leuven, Leuven, Belgium
Katholieke Univ Leuven, Dept Neurosci, Lab Cognit Neurol, Leuven, Belgium
Meersmans, K:
Univ Hosp Leuven, Leuven, Belgium
Katholieke Univ Leuven, Dept Neurosci, Lab Cognit Neurol, Leuven, Belgium
Engelborghs, S:
VUB, Ctr Neurosci, Brussels, Belgium
Univ Antwerp, Reference Ctr Biol Markers Dementia BIODEM, Antwerp, Belgium
Univ Antwerp, Inst Born Bunge, Antwerp, Belgium
VUB Univ Hosp Brussels UZ Brussel, Dept Neurol, Brussels, Belgium
De Roeck, EE:
VUB, Ctr Neurosci, Brussels, Belgium
Univ Antwerp, Reference Ctr Biol Markers Dementia BIODEM, Antwerp, Belgium
Univ Antwerp, Inst Born Bunge, Antwerp, Belgium
Sleegers, K:
Univ Antwerp, Inst Born Bunge, Antwerp, Belgium
VIB, Ctr Mol Neurol, Neurodegenerat Brain Dis Grp, Edegem, Belgium
Frisoni, GB:
Univ Geneva, Geneva, Switzerland
IRCCS Ist Ctr San Giovanni di Dio Fatebenefratell, Brescia, Italy
Blin, O:
AIX Marseille Univ, INS, Ap Hm, Marseille, France
Richardson, JC:
GlaxoSmithKline R&D, Neurosci Therapeut Area, Stevenage, Herts, England
Bordet, R:
Univ Lille, INSERM, CHU Lille, Lille, France
Molinuevo, JL:
Hopsital Clin, IDIBAPS, Alzheimers Dis & Other Cognit Disorders Unit, Barcelona, Spain
Univ Pompeu Fabra, Barcelona Beta Brain Res Ctr, Barcelona, Spain
Rami, L:
Univ Pompeu Fabra, Barcelona Beta Brain Res Ctr, Barcelona, Spain
Wallin, A:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Gothenburg, Sweden
Kettunen, P:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Gothenburg, Sweden
Univ Oxford, Nuffield Dept Clin Neurosci, Oxford, England
Tsolaki, M:
AHEPA Univ Hosp, Dept Neurol 1, Thessaloniki, Greece
Verhey, F:
Maastricht Univ, Alzheimer Ctr Limburg, Sch Mental Hlth & Neurosci, Dept Psychiat & Neuropsychol, Maastricht, Netherlands
Lleo, A:
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Alcolea, D:
Hosp Santa Creu & Sant Pau, Dept Neurol, Barcelona, Spain
Popp, J:
Univ Hosp Lausanne, Lausanne, Switzerland
Geneva Univ Hosp, Dept Mental Hlth & Psychiat, Geriatr Psychiat, Geneva, Switzerland
Peyratout, G:
Univ Hosp Lausanne, Lausanne, Switzerland
Martinez-Lage, P:
CITA Alzheimer Fdn, San Sebastian, Spain
Tainta, M:
CITA Alzheimer Fdn, San Sebastian, Spain
Johannsen, P:
Copenhagen Univ Hosp, Rigshosp, Danish Dementia Res Ctr, Copenhagen, Denmark
Teunissen, CE:
Vrije Univ, Amsterdam Univ Med Ctr, Amsterdam Neurosci, Neurochem Lab,Dept Clin Chem, Amsterdam, Netherlands
Freund-Levi, Y:
Karolinska Inst, Div Clin Geriatr, Dept Neurobiol Caring Sci & Soc NVS, Stockholm, Sweden
Karolinska Univ Hosp Huddinge, Dept Geriatr Med, Stockholm, Sweden
Orebro Univ, Fac Med & Hlth, Dept Psychiat Reg Orebro Cty, Orebro, Sweden
Orebro Univ, Fac Med & Hlth, Sch Med Sci, Orebro, Sweden
Kings Coll London, Dept Old Age Psychiat Psychol & Neurosci, London, England
Frolich, L:
Heidelberg Univ, Zent Inst Seel Gesundheit, Dept Geriatr Psychiat, Mannheim, Germany
Legido-Quigley, C:
Kings Coll London, London, England
Steno Diabet Ctr, Syst Med Grp, Gentofte, Denmark
Barkhof, F:
Vrije Univ Amsterdam Med Ctr, Dept Radiol & Nucl Med, Amsterdam, Netherlands
UCL Inst Neurol & Healthcare Engn, London, England
Blennow, K:
Univ Gothenburg, Dept Psychiat & Neurochem, Molndal, Sweden
Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden
Zetterberg, H:
Univ Gothenburg, Dept Psychiat & Neurochem, Molndal, Sweden
Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden
UCL, UK Dementia Res Inst, London, England
UCL Inst Neurol, Dept Neurodegenerat Dis, London, England
Baker, S:
Janssen R&D, Titusville, NJ USA
Morgan, BP:
Cardiff Univ, Dementia Res Inst Cardiff, Cardiff, S Glam, Wales
Streffer, J:
Univ Antwerp, Reference Ctr Biol Markers Dementia BIODEM, Antwerp, Belgium
Janssen R&D LLC, Beerse, Belgium
Visser, PJ:
Maastricht Univ, Alzheimer Ctr Limburg, Sch Mental Hlth & Neurosci, Dept Psychiat & Neuropsychol, Maastricht, Netherlands
Vrije Univ Amsterdam Med Ctr, Alzheimer Ctr, Amsterdam, Netherlands
Karolinska Inst, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden
Bertram, L:
Univ Lubeck, Inst Neurogenet, Lubeck Interdisciplinary Platform Genome Analyt L, Lubeck, Germany
Univ Lubeck, Inst Cardiogenet, Lubeck Interdisciplinary Platform Genome Analyt L, Lubeck, Germany
Univ Oslo, Dept Psychol, Oslo, Norway
Lovestone, S:
Univ Oxford, Dept Psychiat, Oxford, England
Janssen Cilag UK, Oxford, England
Nevado-Holgado, AJ:
Univ Oxford, Dept Psychiat, Oxford, England
Hybrid Gold, Green Published, Green Accepted
|