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 -
