Replication study of plasma proteins relating to Alzheimer's pathology
Por:
Shi, L, Winchester, LM, Westwood, S, Baird, AL, Anand, SN, Buckley, NJ, Hye, A, Ashton, NJ, Bos, I, Vos, SJB, 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, Barkhof, F, Andreasson, U, Blennow, K, Zetterberg, H, Streffer, J, Lill, CM, Bertram, L, Visser, PJ, Kolb, HC, Narayan, VA, Lovestone, S, Nevado-Holgado, AJ
Publicada:
1 sep 2021
Ahead of Print:
1 mar 2021
Resumen:
Introduction 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.
Methods 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.
Results 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 epsilon 4 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.
Discussion Our study suggests that blood proteins can predict the presence of AD pathology as measured in the ATN framework as well as clinical diagnosis.
Filiaciones:
Shi, L:
Univ Oxford, Dept Psychiat, Oxford, England
Winchester, LM:
Univ Oxford, Dept Psychiat, Oxford, England
Westwood, S:
Univ Oxford, Dept Psychiat, Oxford, England
Baird, AL:
Univ Oxford, Dept Psychiat, Oxford, England
Anand, SN:
Univ Oxford, Dept Psychiat, Oxford, England
Buckley, NJ:
Univ Oxford, Dept Psychiat, Oxford, England
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, Sahlgrenska Acad, Dept Psychiat & Neurochem, Molndal, Sweden
Univ Gothenburg, Wallenberg Ctr Mol & Translat Med, Gothenburg, Sweden
Bos, I:
Maastricht Univ, Sch Mental Hlth & Neurosci, Dept Psychiat & Neuropsychol, Alzheimer Ctr Limburg, Maastricht, Netherlands
Vos, SJB:
Maastricht Univ, Sch Mental Hlth & Neurosci, Dept Psychiat & Neuropsychol, Alzheimer Ctr Limburg, Maastricht, Netherlands
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 Univ Med Ctr, Dept Clin Chem, Neurochem Lab, 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
Vrije Univ Brussel, Dept Neurol, UZ Brussel, Brussels, Belgium
Meersmans, K:
Katholieke Univ Leuven, Lab Cognit Neurol, Dept Neurosci, Leuven, Belgium
Vrije Univ Brussel, Dept Neurol, UZ Brussel, Brussels, Belgium
Engelborghs, S:
Univ Antwerp, Inst Born Bunge, Reference Ctr Biol Markers Dementia BIODEM, Antwerp, Belgium
Vrije Univ Brussel, Dept Neurol, UZ Brussel, Brussels, Belgium
Vrije Univ Brussel, Ctr Neuroci C4N, Brussels, Belgium
Hosp Network Antwerp ZNA Middelheim & Hoge Beuken, Dept Neurol, Antwerp, Belgium
De Roeck, EE:
Univ Antwerp, Inst Born Bunge, Reference Ctr Biol Markers Dementia BIODEM, Antwerp, Belgium
Hosp Network Antwerp ZNA Middelheim & Hoge Beuken, Memory Clin, Antwerp, Belgium
Sleegers, K:
VIB Ctr Mol Neurol, Complex Genet Grp, Antwerp, Belgium
Univ Antwerp, Inst Born Bunge, Dept Biomed Sci, Antwerp, Belgium
Frisoni, GB:
Univ Geneva, Geneva, Switzerland
IRCCS Ist Ctr San Giovanni Dio Fatebenefratelli, Brescia, Italy
Blin, O:
Marseille Univ, INS, AP HM, Marseille, France
Richardson, JC:
GlaxoSmithKline R, 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
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, Sahlgrenska Acad, Inst Neurosci & Physiol, Gothenburg, Sweden
Kettunen, P:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Gothenburg, Sweden
Tsolaki, M:
AHEPA Univ Hosp, Dept Neurol 1, Thessaloniki, Greece
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, Danish Dementia Res Ctr, Rigshosp, Copenhagen, Denmark
Freund-Levi, Y:
Orebro Univ, Sch Med Sci, Div Clin Geriatr, Karolinska Inst,Ctr Alzheimer Res, Stockholm, Sweden
Frolich, L:
Caring Sci & Soc NVS, Dept Neurobiol, Stockholm, Sweden
Dobricic, V:
Heidelberg Univ, Dept Geriatr Psychiat, Zent Inst Seel Gesundheit, Mannheim, Germany
Legido-Quigley, C:
Univ Lubeck, Analyt Inst Neurogenet & Cardiogenet, Lubeck Interdisciplinary Platform Genome Analyt, Lubeck, Germany
Kings Coll London, London, England
Barkhof, F:
Syst Med Grp, Steno Diabet Ctr, Gentofte, Denmark
Vrije Univ Amsterdam, Dept Radiol & Nucl Med, Med Ctr, Amsterdam, Netherlands
Andreasson, U:
UCL Inst Neurol & Healthcare Engn, London, England
Blennow, K:
UCL Inst Neurol & Healthcare Engn, London, England
Zetterberg, H:
UCL Inst Neurol & Healthcare Engn, London, England
Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden
UCL, UK Dementia Res Inst, London, England
UCL Inst Neurol, Dept Neurodegenerat Dis, London, England
Streffer, J:
UCB, Braine Lalleud, Belgium
Lill, CM:
Janssen R&D LLC Beerse, Beerse, Belgium
Univ Lubeck, Dept Surg, Sect Translat Surg Oncol & Biobanking, Campus Lubeck, Lubeck, Germany
Univ Med Ctr Schleswig Holstein, Campus Lubeck, Lubeck, Germany
Imperial Coll, Sch Publ Hlth, Ageing Epidemiol Res Unit, London, England
Kolb, HC:
Univ Oslo, Dept Psychol, Oslo, Norway
Janssen R&D, Beerse, England
Narayan, VA:
Janssen R&D, Beerse, England
Lovestone, S:
Univ Oslo, Dept Psychol, Oslo, Norway
Janssen R&D, Beerse, England
Nevado-Holgado, AJ:
Univ Oxford, Dept Psychiat, Oxford, England
Green Accepted
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