Inflammatory biomarkers in Alzheimer's disease plasma

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

doi:10.1016/j.jalz.2019.03.007

Inflammatory biomarkers in Alzheimer's disease plasma

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

Institut für Neurogenetik

172 Zitate (Scopus)

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.

Originalsprache	Englisch
Zeitschrift	Alzheimer's and Dementia
Jahrgang	15
Ausgabenummer	6
Seiten (von - bis)	776-787
Seitenumfang	12
ISSN	1552-5260
DOIs	https://doi.org/10.1016/j.jalz.2019.03.007
Publikationsstatus	Veröffentlicht - 06.2019

Fördermittel

This publication incorporates results from the research project entitled “Wellcome Trust Consortium for Neuroimmunology of Mood Disorders and Alzheimer's Disease” which is funded by a grant from the Wellcome Trust (grant number: 104025/Z/14/Z ). A complete list of Consortium members is given in the Annex. The AddNeuroMed and DCR plasma samples were provided by the NIHR Biomedical Research Centre and NIHR Dementia Biomedical Research Unit hosted at Kings College London and South London and Maudsley NHS Foundation Trust and funded by the National Institute for Health Research under its Biomedical Research Centers initiative.

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Querschnittsbereich: Medizinische Genetik

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10.1016/j.jalz.2019.03.007

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@article{aed2270126da4bba8ccfe811bdfbaba9,

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 = "\{NIMA Consortium\} and \{Annex: NIMA–Wellcome Trust Consortium for Neuroimmunology of Mood Disorders and Alzheimer's Disease\} and 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 K{\l}oszewska 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 Wahlund, \{Lars Olof\} 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.\}",

note = "Funding Information: This publication incorporates results from the research project entitled “Wellcome Trust Consortium for Neuroimmunology of Mood Disorders and Alzheimer's Disease” which is funded by a grant from the Wellcome Trust (grant number: 104025/Z/14/Z ). A complete list of Consortium members is given in the Annex. Funding Information: The AddNeuroMed and DCR plasma samples were provided by the NIHR Biomedical Research Centre and NIHR Dementia Biomedical Research Unit hosted at Kings College London and South London and Maudsley NHS Foundation Trust and funded by the National Institute for Health Research under its Biomedical Research Centers initiative. Publisher Copyright: {\textcopyright} 2019 The Authors Copyright: Copyright 2019 Elsevier B.V., All rights reserved.",

year = "2019",

month = jun,

doi = "10.1016/j.jalz.2019.03.007",

language = "English",

volume = "15",

pages = "776--787",

journal = "Alzheimer's and Dementia",

issn = "1552-5260",

publisher = "John Wiley and Sons Inc",

number = "6",

}

TY - JOUR

T1 - Inflammatory biomarkers in Alzheimer's disease plasma

AU - NIMA Consortium

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

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.

N1 - Funding Information: This publication incorporates results from the research project entitled “Wellcome Trust Consortium for Neuroimmunology of Mood Disorders and Alzheimer's Disease” which is funded by a grant from the Wellcome Trust (grant number: 104025/Z/14/Z ). A complete list of Consortium members is given in the Annex. Funding Information: The AddNeuroMed and DCR plasma samples were provided by the NIHR Biomedical Research Centre and NIHR Dementia Biomedical Research Unit hosted at Kings College London and South London and Maudsley NHS Foundation Trust and funded by the National Institute for Health Research under its Biomedical Research Centers initiative. Publisher Copyright: © 2019 The Authors Copyright: Copyright 2019 Elsevier B.V., All rights reserved.

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.

UR - https://www.scopus.com/pages/publications/85064805360

U2 - 10.1016/j.jalz.2019.03.007

DO - 10.1016/j.jalz.2019.03.007

M3 - Journal articles

C2 - 31047856

AN - SCOPUS:85064805360

SN - 1552-5260

VL - 15

SP - 776

EP - 787

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - 6

ER -

Inflammatory biomarkers in Alzheimer's disease plasma

Abstract

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UN SDGs

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Dokumente

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