Inflammatory biomarkers in Alzheimer's disease plasma

Morgan, A. R.; Touchard, S.; Leckey, C.; O'Hagan, C.; Nevado-Holgado, A. J.; Barkhof, F.; Bertram, L.; Blin, O.; Bos, I.; Dobricic, V.; Engelborghs, S.; Frisoni, G.; Frolich, L.; Gabel, S.; Johannsen, P.; Kettunen, P.; Kloszewska, I.; Legido-Quigley, C.; Lleo, A.; Martinez-Lage, P.; Mecocci, P.; Meersmans, K.; Molinuevo, J. L.; Peyratout, G.; Popp, J.; Richardson, J.; Sala, I.; Scheltens, P.; Streffer, J.; Soininen, H.; Tainta-Cuezva, M.; Teunissen, C.; Tsolaki, M.; Vandenberghe, R.; Visser, P. J.; Vos, S.; Wahlund, L. -O.; Wallin, A.; Westwood, S.; Zetterberg, H.; Lovestone, S.; Morgan, B. P.; Bullmore, E. T.; Bhatti, J.; Chamberlain, S. J.; Correia, M. M.; Crofts, A. L.; Dickinson, A.; Foster, A. C.; Kitzbichler, M. G.; Knight, C.; Lynall, M. -E.; Maurice, C.; O'Donnell, C.; Pointon, L. J.; St George Hyslop, P.; Turner, L.; Vertes, P.; Widmer, B.; Williams, G. B.; Leckey, C. A.; Cavanagh, J.; Deith, C.; Farmer, S.; Mcclean, J.; Mccoll, A.; Mcpherson, A.; Scouller, P.; Sutherland, M.; Boddeke, H. W. G. M.; Richardson, J. C.; Khan, S.; Murphy, P.; Parker, C. A.; Patel, J.; Jones, D.; de Boer, P.; Kemp, J.; Drevets, W. C.; Nye, J. S.; Wittenberg, G.; Isaac, J.; Bhattacharya, A.; Carruthers, N.; Kolb, H.; Pariante, C. M.; Turkheimer, F.; Barker, G. J.; Byrom, H.; Cash, D.; Cattaneo, A.; Gee, A.; Hastings, C.; Mariani, N.; Mclaughlin, A.; Mondelli, V.; Nettis, M.; Nikkheslat, N.; Randall, K.; Sheridan, H.; Simmons, C.; Singh, N.; Van Loo, V.; Vicente-Rodriguez, M.; Wood, T. C.; Worrell, C.; Zajkowska, Z.; Plath, N.; Egebjerg, J.; Eriksson, H.; Gastambide, F.; Adams, K. H.; Jeggo, R.; Thomsen, C.; Pederson, J. T.; Campbell, B.; Moller, T.; Nelson, B.; Zorn, S.; O'Connor, J.; Attenburrow, M. J.; Baird, A.; Benjamin, J.; Clare, S.; Cowen, P.; Huang, I. -S. D.; Hurley, S.; Jones, H.; Mada, F.; Nevado-Holgado, A.; Oladejo, A.; Ribe, E.; Smith, K.; Vyas, A.; Hughes, Z.; Balice-Gordon, R.; Duerr, J.; Piro, J. R.; Sporn, J.; Perry, V. H.; Cleal, M.; Fryatt, G.; Gomez-Nicola, D.; Mancuso, R.; Reynolds, R.; Harrison, N. A.; Cercignani, M.; Clarke, C. L.; Hoskins, E.; Kohn, C.; Murray, R.; Wilcock, L.; Wlazly, D.; Mount, H.

doi:10.1016/j.jalz.2019.03.007

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.