Validation of Plasma Proteomic Biomarkers Relating to Brain Amyloid Burden in the EMIF-Alzheimer's Disease Multimodal Biomarker Discovery Cohort
Por:
Westwood, S, Baird, AL, Anand, SN, Nevado-Holgado, AJ, Kormilitzin, A, Shi, L, Hye, A, Ashton, NJ, Morgan, AR, Bos, I, Vos, SJB, Baker, S, Buckley, NJ, Ten Kate, M, Scheltens, P, Teunissen, CE, 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, Sala, I, Popp, J, Peyratout, G, Martinez-Lage, P, Tainta, M, Johannsen, P, Freund-Levi, Y, Frolich, L, Dobricic, V, Legido-Quigley, C, Bertram, L, Barkhof, F, Zetterberg, H, Morgan, BP, Streffer, J, Visser, PJ, Lovestone, S
Publicada:
1 ene 2020
Resumen:
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 epsilon 4 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.
Filiaciones:
Westwood, S:
Univ Oxford, Dept Psychiat, Oxford, England
Baird, AL:
Univ Oxford, Dept Psychiat, Oxford, England
Anand, SN:
Univ Oxford, Dept Psychiat, Oxford, England
Nevado-Holgado, AJ:
Univ Oxford, Dept Psychiat, Oxford, England
Kormilitzin, A:
Univ Oxford, Dept Psychiat, Oxford, England
Shi, L:
Univ Oxford, Dept Psychiat, Oxford, England
Hye, A:
Kings Coll London, Maurice Wohl Clin Neurosci, Inst Psychiat Psychol & Neurosci, London, England
Ashton, NJ:
Kings Coll London, Maurice Wohl Clin Neurosci, Inst Psychiat Psychol & Neurosci, London, England
Univ Gothenburg, Dept Psychiat & Neurochem, Molndal, Sweden
Univ Gothenburg, Wallenberg Ctr Mol & Translat Med, Gothenburg, Sweden
Morgan, AR:
Cardiff Univ, Dementia Res Inst Cardiff, Cardiff, Wales
Bos, I:
Maastricht Univ, Alzheimer Ctr Limburg, Sch Mental Hlth & Neurosci, Dept Psychiatty & Neuropsychol, Maastricht, Netherlands
Vos, SJB:
Maastricht Univ, Alzheimer Ctr Limburg, Sch Mental Hlth & Neurosci, Dept Psychiatty & Neuropsychol, Maastricht, Netherlands
Baker, S:
Janssen R&D, Titusville, NJ USA
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
Teunissen, CE:
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, Lab Cognit Neurol, Dept Neurosci, Leuven, Belgium
Meersmans, K:
Univ Hosp Leuven, Leuven, Belgium
Katholieke Univ Leuven, Lab Cognit Neurol, Dept Neurosci, Leuven, Belgium
Engelborghs, S:
Univ Antwerp, Hosp Network Antwerp ZNA Middelheim & Hoge Beuken, Dept Neurol & Memory Clin, Antwerp, Belgium
Vrije Univ Brussel, Ctr Neurosci, Brussels, Belgium
De Roeck, EE:
Univ Antwerp, Hosp Network Antwerp ZNA Middelheim & Hoge Beuken, Dept Neurol & Memory Clin, Antwerp, Belgium
Vrije Univ Brussel, Ctr Neurosci, Brussels, Belgium
Sleegers, K:
Vrije Univ Brussel, Ctr Neurosci, Brussels, Belgium
VIB, Ctr Mol Neurol, Neurodegenerat Brain Dis Grp, Brussels, Belgium
Frisoni, GB:
Univ Geneva, Geneva, Switzerland
IRCCS Ist Ctr San Giovanni Dio Fatebenefratelli, Brescia, Italy
Blin, O:
AIX Marseille Univ, AP HM, INS, Marseille, France
Richardson, JC:
GlaxoSmithKline R&D, Neurosci Therapeut Area, Stevenage, Herts, England
Bordet, R:
Univ Lille, CHU Lille, INSERM, Lille, France
Molinuevo, JL:
Hops Clin IDIBAPS, Alzheimers Dis & Other Cognit Disorders Unit, Barcelona, Spain
Unversitat Pompeu Fabra, Barcelona Beta Brain Res Ctr, Barcelona, Spain
Rami, L:
Unversitat Pompeu Fabra, Barcelona Beta Brain Res Ctr, Barcelona, Spain
Wallin, A:
Univ Gothenburg, Inst Neurosci & Physiol, Sahlgrenska Acad, Gothenburg, Sweden
Kettunen, P:
Univ Gothenburg, Inst Neurosci & Physiol, Sahlgrenska Acad, Gothenburg, Sweden
Tsolaki, M:
Ahepa Univ Hosp, Dept Neurol 1, Makedonia, Thessaloniki, Greece
Verhey, F:
Maastricht Univ, Alzheimer Ctr Limburg, Sch Mental Hlth & Neurosci, Dept Psychiatty & Neuropsychol, Maastricht, Netherlands
Lleo, A:
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Sala, I:
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
Freund-Levi, Y:
Kings Coll London, Maurice Wohl Clin Neurosci, Inst Psychiat Psychol & Neurosci, London, England
Karolinska Inst, Dept Neurobiol, Caring Sci & Soc NVS, Div Clin Geriatr, Stockholm, Sweden
Karolinska Univ Hosp Huddinge, Dept Geriatr Med, Stockholm, Sweden
Frolich, L:
Heidelberg Univ, Zent Inst Seel Gesundheit, Dept Geriatr Psychiat, Mannheim, Germany
Dobricic, V:
Univ Lubeck, Inst Neurogenet & Cardiogenet, Lubeck Interdisciplinary Platform Genome Analyt, Liibeck, Germany
Legido-Quigley, C:
Kings Coll London, London, England
Steno Diabet Ctr, Syst Med Grp, Gentofte, Denmark
Bertram, L:
Univ Lubeck, Inst Neurogenet & Cardiogenet, Lubeck Interdisciplinary Platform Genome Analyt, Liibeck, Germany
Univ Oslo, Dept Psychol, Oslo, Norway
Barkhof, F:
Vrije Univ Amsterdam, Dept Radiol & Nucl Med, Med Ctr, Amsterdam, Netherlands
UCL Inst Neurol & Healthcare Engn, London, England
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
Morgan, BP:
Cardiff Univ, Dementia Res Inst Cardiff, Cardiff, Wales
Streffer, J:
Vrije Univ Brussel, Ctr Neurosci, Brussels, Belgium
UCB, Braine Lalleud, Belgium
Janssen R&D LLC, Beerse, Belgium
Visser, PJ:
Maastricht Univ, Alzheimer Ctr Limburg, Sch Mental Hlth & Neurosci, Dept Psychiatty & Neuropsychol, Maastricht, Netherlands
Vrije Univ Amsterdam Med Ctr, Alzheimer Ctr, Amsterdam, Netherlands
Lovestone, S:
Univ Oxford, Dept Psychiat, Oxford, England
Janssen R&D, Wycombe, England
Green Published, Bronze, Green Accepted
|