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Inflammatory biomarkers in Alzheimer's disease plasma

Morgan AR, Touchard S, Leckey C, O'Hagan C, Nevado-Holgado AJ; NIMA Consortium, Barkhof F, Bertram L, Blin O, Bos I, Dobricic V, Engelborghs S, Frisoni G, Frölich L, Gabel S, Johannsen P, Kettunen P, Kłoszewska I, Legido-Quigley C, Lleó A, Martinez-Lage P, Mecocci P, Meersmans K, Molinuevo JL, Peyratout G, Popp J, Richardson J, Sala I, Scheltens P, Streffer J, Soininen H, Tainta-Cuezva M, Teunissen C, Tsolaki M, Vandenberghe R, Visser PJ, Vos S, Wahlund LO, Wallin A, Westwood S, Zetterberg H, Lovestone S, Morgan BP, Annex:NIMA–Wellcome Trust Consortium for Neuroimmunology of Mood Disorders and Alzheimer's Disease

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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Reference

Morgan AR, Touchard S, Leckey C, O'Hagan C, Nevado-Holgado AJ; NIMA Consortium, Barkhof F, Bertram L, Blin O, Bos I, Dobricic V, Engelborghs S, Frisoni G, Frölich L, Gabel S, Johannsen P, Kettunen P, Kłoszewska I, Legido-Quigley C, Lleó A, Martinez-Lage P, Mecocci P, Meersmans K, Molinuevo JL, Peyratout G, Popp J, Richardson J, Sala I, Scheltens P, Streffer J, Soininen H, Tainta-Cuezva M, Teunissen C, Tsolaki M, Vandenberghe R, Visser PJ, Vos S, Wahlund LO, Wallin A, Westwood S, Zetterberg H, Lovestone S, Morgan BP; Annex:NIMA–Wellcome Trust Consortium for Neuroimmunology of Mood Disorders and Alzheimer's Disease. Inflammatory biomarkers in Alzheimer's disease plasma. Alzheimers Dement. 2019 Apr 29. pii: S1552-5260(19)30078-0. doi:10.1016/j.jalz.2019.03.007