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Inflammatory biomarkers in Alzheimer's disease plasma.

Alzheimer's & dementia : the journal of the Alzheimer's Association (2019-05-03)
Angharad R Morgan, Samuel Touchard, Claire Leckey, Caroline O'Hagan, Alejo J Nevado-Holgado, Frederik Barkhof, Lars Bertram, Olivier Blin, Isabelle Bos, Valerija Dobricic, Sebastiaan Engelborghs, Giovanni Frisoni, Lutz Frölich, Silvey Gabel, Peter Johannsen, Petronella Kettunen, Iwona Kłoszewska, Cristina Legido-Quigley, Alberto Lleó, Pablo Martinez-Lage, Patrizia Mecocci, Karen Meersmans, José Luis Molinuevo, Gwendoline Peyratout, Julius Popp, Jill Richardson, Isabel Sala, Philip Scheltens, Johannes Streffer, Hikka Soininen, Mikel Tainta-Cuezva, Charlotte Teunissen, Magda Tsolaki, Rik Vandenberghe, Pieter Jelle Visser, Stephanie Vos, Lars-Olof Wahlund, Anders Wallin, Sarah Westwood, Henrik Zetterberg, Simon Lovestone, B Paul Morgan
PMID31047856
ABSTRACT

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. 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. 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). Plasma markers of inflammation and complement dysregulation support diagnosis and outcome prediction in AD and MCI. Further replication is needed before clinical translation.