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Alzheimers & Dementia

Publication date: 2019-06-01
Volume: 15 Pages: 776 - 787
Publisher: Elsevier

Author:

Morgan, Angharad R
Touchard, Samuel ; Leckey, Claire ; O'Hagan, Caroline ; Nevado-Holgado, Alejo J ; Barkhof, Frederik ; Bertram, Lars ; Blin, Olivier ; Bos, Isabelle ; Dobricic, Valerija ; Engelborghs, Sebastiaan ; Frisoni, Giovanni ; Froelich, Lutz ; Gabel, Silvey ; Johannsen, Peter ; Kettunen, Petronella ; Koszewska, Iwona ; Legido-Quigley, Cristina ; Lleo, Alberto ; Martinez-Lage, Pablo ; Mecocci, Patrizia ; Meersmans, Karen ; Luis Molinuevo, Jose ; Peyratout, Gwendoline ; Popp, Julius ; Richardson, Jill ; Sala, Isabel ; Scheltens, Philip ; Streffer, Johannes ; Soininen, Hikka ; Tainta-Cuezva, Mikel ; Teunissen, Charlotte ; Tsolaki, Magda ; Vandenberghe, Rik ; Visser, Pieter Jelle ; Vos, Stephanie ; Wahlund, Lars-Olof ; Wallin, Anders ; Westwood, Sarah ; Zetterberg, Henrik ; Lovestone, Simon ; Morgan, B Paul ; Bullmore, Edward T ; Bhatti, Junaid ; Chamberlain, Samuel J ; Correia, Marta M ; Crofts, Anna L ; Dickinson, Amber ; Foster, Andrew C ; Kitzbichler, Manfred G ; Knight, Clare ; Lynall, Mary-Ellen ; Maurice, Christina ; O'Donnell, Ciara ; Pointon, Linda J ; Hyslop, Peter St George ; Turner, Lorinda ; Vertes, Petra ; Widmer, Barry ; Williams, Guy B ; Morgan, B Paul ; Leckey, ClaireA ; Morgan, Angharad R ; O'Hagan, Caroline ; Touchard, Samuel ; Cavanagh, Jonathan ; Deith, Catherine ; Farmer, Scott ; McClean, John ; McColl, Alison ; McPherson, Andrew ; Scouller, Paul ; Sutherland, Murray ; Boddeke, HWGM Erik ; Richardson, Jill C ; Khan, Shahid ; Murphy, Phil ; Parker, Christine A ; Patel, Jai ; Jones, Declan ; de Boer, Peter ; Kemp, John ; Drevets, Wayne C ; Nye, Jeffrey S ; Wittenberg, Gayle ; Isaac, John ; Bhattacharya, Anindya ; Carruthers, Nick ; Kolb, Hartmuth ; Pariante, Carmine M ; Turkheimer, Federico ; Barker, Gareth J ; Byrom, Heidi ; Cash, Diana ; Cattaneo, Annamaria ; Gee, Antony ; Hastings, Caitlin ; Mariani, Nicole ; McLaughlin, Anna ; Mondelli, Valeria ; Nettis, Maria ; Nikkheslat, Naghmeh ; Randall, Karen ; Sheridan, Hannah ; Simmons, Camilla ; Singh, Nisha ; Van Loo, Victoria ; Vicente-Rodriguez, Marta ; Wood, Tobias C ; Worrell, Courtney ; Zajkowska, Zuzanna ; Plath, Niels ; Egebjerg, Jan ; Eriksson, Hans ; Gastambide, Francois ; Adams, Karen Husted ; Jeggo, Ross ; Thomsen, Christian ; Pederson, Jan Torleif ; Campbell, Brian ; Moller, Thomas ; Nelson, Bob ; Zorn, Stevin ; O'Connor, Jason ; Attenburrow, Mary Jane ; Baird, Alison ; Benjamin, Jithen ; Clare, Stuart ; Cowen, Philip ; Huang, I-Shu Dante ; Hurley, Samuel ; Jones, Helen ; Lovestone, Simon ; Mada, Francisca ; Nevado-Holgado, Alejo ; Oladejo, Akintayo ; Ribe, Elena ; Smith, Katy ; Vyas, Anviti ; Hughes, Zoe ; Balice-Gordon, Rita ; Duerr, James ; Piro, Justin R ; Sporn, Jonathan ; Perry, V Hugh ; Cleal, Madeleine ; Fryatt, Gemma ; Gomez-Nicola, Diego ; Mancuso, Renzo ; Reynolds, Richard ; Harrison, Neil A ; Cercignani, Mara ; Clarke, Charlotte L ; Hoskins, Elizabeth ; Kohn, Charmaine ; Murray, Rosemary ; Wilcock, Lauren ; Wlazly, Dominika

Keywords:

Science & Technology, Life Sciences & Biomedicine, Clinical Neurology, Neurosciences & Neurology, 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, Aged, Alzheimer Disease, Amyloid beta-Peptides, Biomarkers, Cognitive Dysfunction, Cohort Studies, Complement Factor B, Complement Factor H, Humans, Internationality, Prognosis, NIMA Consortium, Annex: NIMA–Wellcome Trust Consortium for Neuroimmunology of Mood Disorders and Alzheimer's Disease, 1103 Clinical Sciences, 1109 Neurosciences, Geriatrics, 3202 Clinical sciences, 3209 Neurosciences, 5202 Biological psychology

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.