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.

Inflammatory biomarkers in Alzheimer's disease plasma / A.R. Morgan, S. Touchard, C. Leckey, C. O'Hagan, A.J. Nevado-Holgado, F. Barkhof, L. Bertram, O. Blin, I. Bos, V. Dobricic, S. Engelborghs, G. Frisoni, L. Frolich, S. Gabel, P. Johannsen, P. Kettunen, I. Kloszewska, C. Legido-Quigley, A. Lleo, P. Martinez-Lage, P. Mecocci, K. Meersmans, J.L. Molinuevo, G. Peyratout, J. Popp, J. Richardson, I. Sala, P. Scheltens, J. Streffer, H. Soininen, M. Tainta-Cuezva, C. Teunissen, M. Tsolaki, R. Vandenberghe, P.J. Visser, S. Vos, L.-. Wahlund, A. Wallin, S. Westwood, H. Zetterberg, S. Lovestone, B.P. Morgan, E.T. Bullmore, J. Bhatti, S.J. Chamberlain, M.M. Correia, A.L. Crofts, A. Dickinson, A.C. Foster, M.G. Kitzbichler, C. Knight, M.-. Lynall, C. Maurice, C. O'Donnell, L.J. Pointon, P. St George Hyslop, L. Turner, P. Vertes, B. Widmer, G.B. Williams, C.A. Leckey, J. Cavanagh, C. Deith, S. Farmer, J. Mcclean, A. Mccoll, A. Mcpherson, P. Scouller, M. Sutherland, H.W.G.M. Boddeke, J.C. Richardson, S. Khan, P. Murphy, C.A. Parker, J. Patel, D. Jones, P. de Boer, J. Kemp, W.C. Drevets, J.S. Nye, G. Wittenberg, J. Isaac, A. Bhattacharya, N. Carruthers, H. Kolb, C.M. Pariante, F. Turkheimer, G.J. Barker, H. Byrom, D. Cash, A. Cattaneo, A. Gee, C. Hastings, N. Mariani, A. Mclaughlin, V. Mondelli, M. Nettis, N. Nikkheslat, K. Randall, H. Sheridan, C. Simmons, N. Singh, V. Van Loo, M. Vicente-Rodriguez, T.C. Wood, C. Worrell, Z. Zajkowska, N. Plath, J. Egebjerg, H. Eriksson, F. Gastambide, K.H. Adams, R. Jeggo, C. Thomsen, J.T. Pederson, B. Campbell, T. Moller, B. Nelson, S. Zorn, J. O'Connor, M.J. Attenburrow, A. Baird, J. Benjamin, S. Clare, P. Cowen, I.-.D. Huang, S. Hurley, H. Jones, F. Mada, A. Nevado-Holgado, A. Oladejo, E. Ribe, K. Smith, A. Vyas, Z. Hughes, R. Balice-Gordon, J. Duerr, J.R. Piro, J. Sporn, V.H. Perry, M. Cleal, G. Fryatt, D. Gomez-Nicola, R. Mancuso, R. Reynolds, N.A. Harrison, M. Cercignani, C.L. Clarke, E. Hoskins, C. Kohn, R. Murray, L. Wilcock, D. Wlazly, H. Mount. - In: ALZHEIMER'S & DEMENTIA. - ISSN 1552-5260. - 15:6(2019 Jun), pp. 776-787. [10.1016/j.jalz.2019.03.007]

Inflammatory biomarkers in Alzheimer's disease plasma

A. Lleo;C. Maurice;S. Khan;D. Jones;A. Cattaneo;N. Singh;
2019

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.
Alzheimer's disease; Biomarker; Complement; Inflammation; Plasma
Settore BIO/14 - Farmacologia
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/706262
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