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 Froelich, Silvey Gabel, Peter Johannsen, Petronella Kettunen, Iwona Koszewska, Cristina Legido-Quigley, Alberto Lleo, Pablo Martinez-LagePatrizia Mecocci, Karen Meersmans, Jose 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–Wellcome Trust Consortium for Neuroimmunology of Mood Disorders and Alzheimer's Disease

*Corresponding author for this work

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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/APOe4 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. (C) 2019 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Original languageEnglish
Pages (from-to)776-787
Number of pages12
JournalAlzheimer's & Dementia
Volume15
Issue number6
DOIs
Publication statusPublished - Jun 2019

Keywords

  • Alzheimer's disease
  • Biomarker
  • Plasma
  • Inflammation
  • Complement
  • MILD COGNITIVE IMPAIRMENT
  • NONSTEROIDAL ANTIINFLAMMATORY DRUGS
  • GENOME-WIDE ASSOCIATION
  • IMMUNE-SYSTEM
  • CEREBROSPINAL-FLUID
  • IDENTIFIES VARIANTS
  • FACTOR-H
  • COMPLEMENT
  • SERUM
  • RISK

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