Inflammatory biomarkers in Alzheimer's disease plasma

Angharad R. Morgan(UK Dementia Research Institute), Samuel Touchard(UK Dementia Research Institute), Claire A. Leckey(UK Dementia Research Institute), Caroline O’Hagan(UK Dementia Research Institute), Alejo Nevado‐Holgado(University of Oxford), Frederik Barkhof(University College London), Lars Bertram(Max Planck Institute for Molecular Genetics), Olivier Blin(Aix-Marseille Université), Isabelle Bos(Maastricht University), Valerija Dobričić(University of Lübeck), Sebastiaan Engelborghs(Ziekenhuisnetwerk Antwerpen Stuivenberg), Giovanni B. Frisoni(University of Geneva), Lutz Frölich(Heidelberg University), Silvey Gabel(KU Leuven), Peter Johannsen(Karolinska Institutet), Petronella Kettunen(University of Gothenburg), Iwona Kłoszewska(Medical University of Lodz), Cristina Legido‐Quigley(University College London), Alberto Lleó(Hospital de Sant Pau), Pablo Martínez‐Lage(Fundacion CITA Alzheimer), Patrizia Mecocci(University of Perugia), Karen Meersmans(KU Leuven), José Luís Molinuevo(Universitat Pompeu Fabra), Gwendoline Peyratout(University of Lausanne), Julius Popp(University of Geneva), Jill Richardson(GlaxoSmithKline (United Kingdom)), Isabel Sala(Hospital de Sant Pau), Philip Scheltens(Amsterdam University Medical Centers), Johannes Streffer(University of Antwerp), Hikka Soininen(University of Eastern Finland), Mikel Tainta(Fundacion CITA Alzheimer), Charlotte E. Teunissen, Magda Tsolaki(AHEPA University Hospital), Rik Vandenberghe(Amsterdam University Medical Centers), Pieter Jelle Visser(Maastricht University), Stephanie J. B. Vos(Maastricht University), Lars‐Olof Wahlund(Karolinska Institutet), Anders Wallin(University of Gothenburg), Sarah Westwood(University of Oxford), Henrik Zetterberg(Sahlgrenska University Hospital), Simon Lovestone(University of Oxford), B. Paul Morgan(UK Dementia Research Institute)
Alzheimer s & Dementia
April 29, 2019
10.1016/j.jalz.2019.03.007
Cited by 206Open Access
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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/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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