Inflammatory biomarkers in Alzheimer's disease plasma

Angharad R. Morgan, Samuel Touchard, Claire Leckey, Caroline O'Hagan, Alejo J. Nevado-Holgado, Frederik Barkhof, Lars Bertram, Olivier Blin, Isabelle Bos, Valerija Dobricic, Sebastiaan Engelborghs, Giovanni Frisoni, Lutz Frölich, Silvey Gabel, Peter Johannsen, Petronella Kettunen, Iwona Kłoszewska, Cristina Legido-Quigley, Alberto Lleó, Pablo Martinez-Lage & 32 others Patrizia Mecocci, Karen Meersmans, José Luis Molinuevo, Gwendoline Peyratout, Julius Popp, Jill Richardson, Isabel Sala, Philip Scheltens, Johannes Streffer, Hikka Soininen, Mikel Tainta-Cuezva, Charlotte Teunissen, Magda Tsolaki, Rik Vandenberghe, Pieter Jelle Visser, Stephanie Vos, Lars-Olof Wahlund, Anders Wallin, Sarah Westwood, Henrik Zetterberg, Simon Lovestone, B. Paul Morgan, Edward T. Bullmore, Junaid Bhatti, Samuel J. Chamberlain, Marta M. Correia, Anna L. Crofts, Amber Dickinson, Andrew C. Foster, Manfred G. Kitzbichler, NIMA Consortium, Annex: NIMA–Wellcome Trust Consortium for Neuroimmunology of Mood Disorders and Alzheimer's Disease

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Introduction: Plasma biomarkers for Alzheimer's disease (AD)diagnosis/stratification are a “Holy Grail” of AD research and intensively sought; however, there are no well-established plasma markers. Methods: A hypothesis-led plasma biomarker search was conducted in the context of international multicenter studies. The discovery phase measured 53 inflammatory proteins in elderly control (CTL; 259), mild cognitive impairment (MCI; 199), and AD (262)subjects from AddNeuroMed. Results: Ten analytes showed significant intergroup differences. Logistic regression identified five (FB, FH, sCR1, MCP-1, eotaxin-1)that, age/APOε4 adjusted, optimally differentiated AD and CTL (AUC: 0.79), and three (sCR1, MCP-1, eotaxin-1)that optimally differentiated AD and MCI (AUC: 0.74). These models replicated in an independent cohort (EMIF; AUC 0.81 and 0.67). Two analytes (FB, FH)plus age predicted MCI progression to AD (AUC: 0.71). Discussion: Plasma markers of inflammation and complement dysregulation support diagnosis and outcome prediction in AD and MCI. Further replication is needed before clinical translation.
Original languageEnglish
Pages (from-to)776-787
JournalAlzheimer's and Dementia
Volume15
Issue number6
DOIs
Publication statusPublished - Jun 2019

Cite this

Morgan, A. R., Touchard, S., Leckey, C., O'Hagan, C., Nevado-Holgado, A. J., Barkhof, F., ... Annex: NIMA–Wellcome Trust Consortium for Neuroimmunology of Mood Disorders and Alzheimer's Disease (2019). Inflammatory biomarkers in Alzheimer's disease plasma. Alzheimer's and Dementia, 15(6), 776-787. https://doi.org/10.1016/j.jalz.2019.03.007
Morgan, Angharad R. ; Touchard, Samuel ; Leckey, Claire ; O'Hagan, Caroline ; Nevado-Holgado, Alejo J. ; Barkhof, Frederik ; Bertram, Lars ; Blin, Olivier ; Bos, Isabelle ; Dobricic, Valerija ; Engelborghs, Sebastiaan ; Frisoni, Giovanni ; Frölich, Lutz ; Gabel, Silvey ; Johannsen, Peter ; Kettunen, Petronella ; Kłoszewska, Iwona ; Legido-Quigley, Cristina ; Lleó, Alberto ; Martinez-Lage, Pablo ; Mecocci, Patrizia ; Meersmans, Karen ; Molinuevo, José Luis ; Peyratout, Gwendoline ; Popp, Julius ; Richardson, Jill ; Sala, Isabel ; Scheltens, Philip ; Streffer, Johannes ; Soininen, Hikka ; Tainta-Cuezva, Mikel ; Teunissen, Charlotte ; Tsolaki, Magda ; Vandenberghe, Rik ; Visser, Pieter Jelle ; Vos, Stephanie ; Wahlund, Lars-Olof ; Wallin, Anders ; Westwood, Sarah ; Zetterberg, Henrik ; Lovestone, Simon ; Morgan, B. Paul ; Bullmore, Edward T. ; Bhatti, Junaid ; Chamberlain, Samuel J. ; Correia, Marta M. ; Crofts, Anna L. ; Dickinson, Amber ; Foster, Andrew C. ; Kitzbichler, Manfred G. ; NIMA Consortium ; Annex: NIMA–Wellcome Trust Consortium for Neuroimmunology of Mood Disorders and Alzheimer's Disease. / Inflammatory biomarkers in Alzheimer's disease plasma. In: Alzheimer's and Dementia. 2019 ; Vol. 15, No. 6. pp. 776-787.
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title = "Inflammatory biomarkers in Alzheimer's disease plasma",
abstract = "Introduction: Plasma biomarkers for Alzheimer's disease (AD)diagnosis/stratification are a “Holy Grail” of AD research and intensively sought; however, there are no well-established plasma markers. Methods: A hypothesis-led plasma biomarker search was conducted in the context of international multicenter studies. The discovery phase measured 53 inflammatory proteins in elderly control (CTL; 259), mild cognitive impairment (MCI; 199), and AD (262)subjects from AddNeuroMed. Results: Ten analytes showed significant intergroup differences. Logistic regression identified five (FB, FH, sCR1, MCP-1, eotaxin-1)that, age/APOε4 adjusted, optimally differentiated AD and CTL (AUC: 0.79), and three (sCR1, MCP-1, eotaxin-1)that optimally differentiated AD and MCI (AUC: 0.74). These models replicated in an independent cohort (EMIF; AUC 0.81 and 0.67). Two analytes (FB, FH)plus age predicted MCI progression to AD (AUC: 0.71). Discussion: Plasma markers of inflammation and complement dysregulation support diagnosis and outcome prediction in AD and MCI. Further replication is needed before clinical translation.",
author = "Morgan, {Angharad R.} and Samuel Touchard and Claire Leckey and Caroline O'Hagan and Nevado-Holgado, {Alejo J.} and Frederik Barkhof and Lars Bertram and Olivier Blin and Isabelle Bos and Valerija Dobricic and Sebastiaan Engelborghs and Giovanni Frisoni and Lutz Fr{\"o}lich and Silvey Gabel and Peter Johannsen and Petronella Kettunen and Iwona Kłoszewska and Cristina Legido-Quigley and Alberto Lle{\'o} and Pablo Martinez-Lage and Patrizia Mecocci and Karen Meersmans and Molinuevo, {Jos{\'e} Luis} and Gwendoline Peyratout and Julius Popp and Jill Richardson and Isabel Sala and Philip Scheltens and Johannes Streffer and Hikka Soininen and Mikel Tainta-Cuezva and Charlotte Teunissen and Magda Tsolaki and Rik Vandenberghe and Visser, {Pieter Jelle} and Stephanie Vos and Lars-Olof Wahlund and Anders Wallin and Sarah Westwood and Henrik Zetterberg and Simon Lovestone and Morgan, {B. Paul} and Bullmore, {Edward T.} and Junaid Bhatti and Chamberlain, {Samuel J.} and Correia, {Marta M.} and Crofts, {Anna L.} and Amber Dickinson and Foster, {Andrew C.} and Kitzbichler, {Manfred G.} and {NIMA Consortium} and {Annex: NIMA–Wellcome Trust Consortium for Neuroimmunology of Mood Disorders and Alzheimer's Disease}",
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Morgan, AR, Touchard, S, Leckey, C, O'Hagan, C, Nevado-Holgado, AJ, Barkhof, F, Bertram, L, Blin, O, Bos, I, Dobricic, V, Engelborghs, S, Frisoni, G, Frölich, L, Gabel, S, Johannsen, P, Kettunen, P, Kłoszewska, I, Legido-Quigley, C, Lleó, A, Martinez-Lage, P, Mecocci, P, Meersmans, K, Molinuevo, JL, Peyratout, G, Popp, J, Richardson, J, Sala, I, Scheltens, P, Streffer, J, Soininen, H, Tainta-Cuezva, M, Teunissen, C, Tsolaki, M, Vandenberghe, R, Visser, PJ, Vos, S, Wahlund, L-O, Wallin, A, Westwood, S, Zetterberg, H, Lovestone, S, Morgan, BP, Bullmore, ET, Bhatti, J, Chamberlain, SJ, Correia, MM, Crofts, AL, Dickinson, A, Foster, AC, Kitzbichler, MG, NIMA Consortium & Annex: NIMA–Wellcome Trust Consortium for Neuroimmunology of Mood Disorders and Alzheimer's Disease 2019, 'Inflammatory biomarkers in Alzheimer's disease plasma' Alzheimer's and Dementia, vol. 15, no. 6, pp. 776-787. https://doi.org/10.1016/j.jalz.2019.03.007

Inflammatory biomarkers in Alzheimer's disease plasma. / Morgan, Angharad R.; Touchard, Samuel; Leckey, Claire; O'Hagan, Caroline; Nevado-Holgado, Alejo J.; Barkhof, Frederik; Bertram, Lars; Blin, Olivier; Bos, Isabelle; Dobricic, Valerija; Engelborghs, Sebastiaan; Frisoni, Giovanni; Frölich, Lutz; Gabel, Silvey; Johannsen, Peter; Kettunen, Petronella; Kłoszewska, Iwona; Legido-Quigley, Cristina; Lleó, Alberto; Martinez-Lage, Pablo; Mecocci, Patrizia; Meersmans, Karen; Molinuevo, José Luis; Peyratout, Gwendoline; Popp, Julius; Richardson, Jill; Sala, Isabel; Scheltens, Philip; Streffer, Johannes; Soininen, Hikka; Tainta-Cuezva, Mikel; Teunissen, Charlotte; Tsolaki, Magda; Vandenberghe, Rik; Visser, Pieter Jelle; Vos, Stephanie; Wahlund, Lars-Olof; Wallin, Anders; Westwood, Sarah; Zetterberg, Henrik; Lovestone, Simon; Morgan, B. Paul; Bullmore, Edward T.; Bhatti, Junaid; Chamberlain, Samuel J.; Correia, Marta M.; Crofts, Anna L.; Dickinson, Amber; Foster, Andrew C.; Kitzbichler, Manfred G.; NIMA Consortium; Annex: NIMA–Wellcome Trust Consortium for Neuroimmunology of Mood Disorders and Alzheimer's Disease.

In: Alzheimer's and Dementia, Vol. 15, No. 6, 06.2019, p. 776-787.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Inflammatory biomarkers in Alzheimer's disease plasma

AU - Morgan, Angharad R.

AU - Touchard, Samuel

AU - Leckey, Claire

AU - O'Hagan, Caroline

AU - Nevado-Holgado, Alejo J.

AU - Barkhof, Frederik

AU - Bertram, Lars

AU - Blin, Olivier

AU - Bos, Isabelle

AU - Dobricic, Valerija

AU - Engelborghs, Sebastiaan

AU - Frisoni, Giovanni

AU - Frölich, Lutz

AU - Gabel, Silvey

AU - Johannsen, Peter

AU - Kettunen, Petronella

AU - Kłoszewska, Iwona

AU - Legido-Quigley, Cristina

AU - Lleó, Alberto

AU - Martinez-Lage, Pablo

AU - Mecocci, Patrizia

AU - Meersmans, Karen

AU - Molinuevo, José Luis

AU - Peyratout, Gwendoline

AU - Popp, Julius

AU - Richardson, Jill

AU - Sala, Isabel

AU - Scheltens, Philip

AU - Streffer, Johannes

AU - Soininen, Hikka

AU - Tainta-Cuezva, Mikel

AU - Teunissen, Charlotte

AU - Tsolaki, Magda

AU - Vandenberghe, Rik

AU - Visser, Pieter Jelle

AU - Vos, Stephanie

AU - Wahlund, Lars-Olof

AU - Wallin, Anders

AU - Westwood, Sarah

AU - Zetterberg, Henrik

AU - Lovestone, Simon

AU - Morgan, B. Paul

AU - Bullmore, Edward T.

AU - Bhatti, Junaid

AU - Chamberlain, Samuel J.

AU - Correia, Marta M.

AU - Crofts, Anna L.

AU - Dickinson, Amber

AU - Foster, Andrew C.

AU - Kitzbichler, Manfred G.

AU - NIMA Consortium

AU - Annex: NIMA–Wellcome Trust Consortium for Neuroimmunology of Mood Disorders and Alzheimer's Disease

PY - 2019/6

Y1 - 2019/6

N2 - Introduction: Plasma biomarkers for Alzheimer's disease (AD)diagnosis/stratification are a “Holy Grail” of AD research and intensively sought; however, there are no well-established plasma markers. Methods: A hypothesis-led plasma biomarker search was conducted in the context of international multicenter studies. The discovery phase measured 53 inflammatory proteins in elderly control (CTL; 259), mild cognitive impairment (MCI; 199), and AD (262)subjects from AddNeuroMed. Results: Ten analytes showed significant intergroup differences. Logistic regression identified five (FB, FH, sCR1, MCP-1, eotaxin-1)that, age/APOε4 adjusted, optimally differentiated AD and CTL (AUC: 0.79), and three (sCR1, MCP-1, eotaxin-1)that optimally differentiated AD and MCI (AUC: 0.74). These models replicated in an independent cohort (EMIF; AUC 0.81 and 0.67). Two analytes (FB, FH)plus age predicted MCI progression to AD (AUC: 0.71). Discussion: Plasma markers of inflammation and complement dysregulation support diagnosis and outcome prediction in AD and MCI. Further replication is needed before clinical translation.

AB - Introduction: Plasma biomarkers for Alzheimer's disease (AD)diagnosis/stratification are a “Holy Grail” of AD research and intensively sought; however, there are no well-established plasma markers. Methods: A hypothesis-led plasma biomarker search was conducted in the context of international multicenter studies. The discovery phase measured 53 inflammatory proteins in elderly control (CTL; 259), mild cognitive impairment (MCI; 199), and AD (262)subjects from AddNeuroMed. Results: Ten analytes showed significant intergroup differences. Logistic regression identified five (FB, FH, sCR1, MCP-1, eotaxin-1)that, age/APOε4 adjusted, optimally differentiated AD and CTL (AUC: 0.79), and three (sCR1, MCP-1, eotaxin-1)that optimally differentiated AD and MCI (AUC: 0.74). These models replicated in an independent cohort (EMIF; AUC 0.81 and 0.67). Two analytes (FB, FH)plus age predicted MCI progression to AD (AUC: 0.71). Discussion: Plasma markers of inflammation and complement dysregulation support diagnosis and outcome prediction in AD and MCI. Further replication is needed before clinical translation.

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UR - https://www.ncbi.nlm.nih.gov/pubmed/31047856

U2 - 10.1016/j.jalz.2019.03.007

DO - 10.1016/j.jalz.2019.03.007

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EP - 787

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JF - Alzheimers & Dementia

SN - 1552-5260

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Morgan AR, Touchard S, Leckey C, O'Hagan C, Nevado-Holgado AJ, Barkhof F et al. Inflammatory biomarkers in Alzheimer's disease plasma. Alzheimer's and Dementia. 2019 Jun;15(6):776-787. https://doi.org/10.1016/j.jalz.2019.03.007