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 - O'Connor, Jason
N1 - Publisher Copyright:
© 2019 The Authors
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.
KW - Alzheimer's disease
KW - Biomarker
KW - Complement
KW - Inflammation
KW - Plasma
UR - https://www.scopus.com/pages/publications/85064805360
UR - https://www.scopus.com/pages/publications/85064805360#tab=citedBy
U2 - 10.1016/j.jalz.2019.03.007
DO - 10.1016/j.jalz.2019.03.007
M3 - Article
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 -