Replication study of plasma proteins relating to Alzheimer's pathology

Liu Shi; Laura M. Winchester; Sarah Westwood; Alison L Baird; Sneha N Anand; Noel J. Buckley; Abdul Hye; Nicholas J. Ashton; Isabelle Bos; Stephanie J.B. Vos; Mara Ten Kate; Philip Scheltens; Charlotte E. Teunissen; Rik Vandenberghe; Silvy Gabel; Karen Meersmans; Sebastiaan Engelborghs; Ellen E De Roeck; Kristel Sleegers; Giovanni B. Frisoni; Olivier Blin; Jill C. Richardson; Régis Bordet; José L. Molinuevo; Lorena Rami Gonzalez; Anders Wallin; Petronella Kettunen; Magda Tsolaki; Frans Verhey; Alberto Lleó; Isabel Sala; Julius Popp; Gwendoline Peyratout; Pablo Martinez-Lage; Mikel Tainta; Peter Johannsen; Yvonne Freund-Levi; Lutz Frölich; Valerija Dobricic; Cristina Legido-Quigley; Frederik Barkhof; Ulf Andreasson; Kaj Blennow; Henrik Zetterberg; Johannes Streffer; Christina M. Lill; Lars Bertram; Pieter Jelle Visser; Hartmuth C. Kolb; Vaibhav A. Narayan; Simon Lovestone; Alejo Nevado-Holgado

doi:10.1002/alz.12322

Replication study of plasma proteins relating to Alzheimer's pathology

Liu Shi, Laura M. Winchester, Sarah Westwood, Alison L Baird, Sneha N Anand, Noel J. Buckley, Abdul Hye, Nicholas J. Ashton, Isabelle Bos, Stephanie J.B. Vos, Mara Ten Kate, Philip Scheltens, Charlotte E. Teunissen, Rik Vandenberghe, Silvy Gabel, Karen Meersmans, Sebastiaan Engelborghs, Ellen E De Roeck, Kristel Sleegers, Giovanni B. FrisoniOlivier Blin, Jill C. Richardson, Régis Bordet, José L. Molinuevo, Lorena Rami Gonzalez, Anders Wallin, Petronella Kettunen, Magda Tsolaki, Frans Verhey, Alberto Lleó, Isabel Sala, Julius Popp, Gwendoline Peyratout, Pablo Martinez-Lage, Mikel Tainta, Peter Johannsen, Yvonne Freund-Levi, Lutz Frölich, Valerija Dobricic, Cristina Legido-Quigley, Frederik Barkhof, Ulf Andreasson, Kaj Blennow, Henrik Zetterberg, Johannes Streffer, Christina M. Lill, Lars Bertram, Pieter Jelle Visser, Hartmuth C. Kolb, Vaibhav A. Narayan, Simon Lovestone, Alejo Nevado-Holgado

Departament de Medicina

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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 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. 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.

Idioma original	Anglès
Pàgines (de-a)	1452-1464
Nombre de pàgines	13
Revista	Alzheimer's and Dementia
Volum	17
Número	9
DOIs	https://doi.org/10.1002/alz.12322
Estat de la publicació	Publicada - 2021

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10.1002/alz.12322

https://ddd.uab.cat/record/270313

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https://www.scopus.com/pages/publications/85103432126

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Shi, L., Winchester, L. M., Westwood, S., Baird, A. L., Anand, S. N., Buckley, N. J., Hye, A., Ashton, N. J., Bos, I., Vos, S. J. B., Kate, M. T., Scheltens, P., Teunissen, C. E., Vandenberghe, R., Gabel, S., Meersmans, K., Engelborghs, S., De Roeck, E. E., Sleegers, K., ... Nevado-Holgado, A. (2021). Replication study of plasma proteins relating to Alzheimer's pathology. Alzheimer's and Dementia, 17(9), 1452-1464. https://doi.org/10.1002/alz.12322

@article{37cc3c3f671d44e7a637497cefe3802a,

title = "Replication study of plasma proteins relating to Alzheimer's pathology",

abstract = "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 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. 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.",

keywords = "Alzheimer's disease, ATN framework, Biomarker, Dementia, Network analysis, Plasma proteomics, Replication",

author = "Liu Shi and Winchester, \{Laura M.\} and Sarah Westwood and Baird, \{Alison L\} and Anand, \{Sneha N\} and Buckley, \{Noel J.\} and Abdul Hye and Ashton, \{Nicholas J.\} and Isabelle Bos and Vos, \{Stephanie J.B.\} and Kate, \{Mara Ten\} and Philip Scheltens and Teunissen, \{Charlotte E.\} and Rik Vandenberghe and Silvy Gabel and Karen Meersmans and Sebastiaan Engelborghs and \{De Roeck\}, \{Ellen E\} and Kristel Sleegers and Frisoni, \{Giovanni B.\} and Olivier Blin and Richardson, \{Jill C.\} and R{\'e}gis Bordet and Molinuevo, \{Jos{\'e} L.\} and \{Rami Gonzalez\}, Lorena and Anders Wallin and Petronella Kettunen and Magda Tsolaki and Frans Verhey and Alberto Lle{\'o} and Isabel Sala and Julius Popp and Gwendoline Peyratout and Pablo Martinez-Lage and Mikel Tainta and Peter Johannsen and Yvonne Freund-Levi and Lutz Fr{\"o}lich and Valerija Dobricic and Cristina Legido-Quigley and Frederik Barkhof and Ulf Andreasson and Kaj Blennow and Henrik Zetterberg and Johannes Streffer and Lill, \{Christina M.\} and Lars Bertram and Visser, \{Pieter Jelle\} and Kolb, \{Hartmuth C.\} and Narayan, \{Vaibhav A.\} and Simon Lovestone and Alejo Nevado-Holgado",

year = "2021",

doi = "10.1002/alz.12322",

language = "English",

volume = "17",

pages = "1452--1464",

number = "9",

}

Shi, L, Winchester, LM, Westwood, S, Baird, AL, Anand, SN, Buckley, NJ, Hye, A, Ashton, NJ, Bos, I, Vos, SJB, Kate, MT, 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 Gonzalez, L, Wallin, A, Kettunen, P, Tsolaki, M, Verhey, F, Lleó, A, Sala, I, Popp, J, Peyratout, G, Martinez-Lage, P, Tainta, M, Johannsen, P, Freund-Levi, Y, Frölich, 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, A 2021, 'Replication study of plasma proteins relating to Alzheimer's pathology', Alzheimer's and Dementia, vol. 17, núm. 9, pàg. 1452-1464. https://doi.org/10.1002/alz.12322

TY - JOUR

T1 - Replication study of plasma proteins relating to Alzheimer's pathology

AU - Shi, Liu

AU - Winchester, Laura M.

AU - Westwood, Sarah

AU - Baird, Alison L

AU - Anand, Sneha N

AU - Buckley, Noel J.

AU - Hye, Abdul

AU - Ashton, Nicholas J.

AU - Bos, Isabelle

AU - Vos, Stephanie J.B.

AU - Kate, Mara Ten

AU - Scheltens, Philip

AU - Teunissen, Charlotte E.

AU - Vandenberghe, Rik

AU - Gabel, Silvy

AU - Meersmans, Karen

AU - Engelborghs, Sebastiaan

AU - De Roeck, Ellen E

AU - Sleegers, Kristel

AU - Frisoni, Giovanni B.

AU - Blin, Olivier

AU - Richardson, Jill C.

AU - Bordet, Régis

AU - Molinuevo, José L.

AU - Rami Gonzalez, Lorena

AU - Wallin, Anders

AU - Kettunen, Petronella

AU - Tsolaki, Magda

AU - Verhey, Frans

AU - Lleó, Alberto

AU - Sala, Isabel

AU - Popp, Julius

AU - Peyratout, Gwendoline

AU - Martinez-Lage, Pablo

AU - Tainta, Mikel

AU - Johannsen, Peter

AU - Freund-Levi, Yvonne

AU - Frölich, Lutz

AU - Dobricic, Valerija

AU - Legido-Quigley, Cristina

AU - Barkhof, Frederik

AU - Andreasson, Ulf

AU - Blennow, Kaj

AU - Zetterberg, Henrik

AU - Streffer, Johannes

AU - Lill, Christina M.

AU - Bertram, Lars

AU - Visser, Pieter Jelle

AU - Kolb, Hartmuth C.

AU - Narayan, Vaibhav A.

AU - Lovestone, Simon

AU - Nevado-Holgado, Alejo

PY - 2021

Y1 - 2021

N2 - 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 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. 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.

AB - 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 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. 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.

KW - Alzheimer's disease

KW - ATN framework

KW - Biomarker

KW - Dementia

KW - Network analysis

KW - Plasma proteomics

KW - Replication

UR - https://www.scopus.com/pages/publications/85103432126

U2 - 10.1002/alz.12322

DO - 10.1002/alz.12322

M3 - Article

C2 - 33792144

SN - 1552-5260

VL - 17

SP - 1452

EP - 1464

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - 9

ER -

Replication study of plasma proteins relating to Alzheimer's pathology

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