Replication study of plasma proteins relating to Alzheimer's pathology
Liu Shi, Laura Winchester, Sarah Westwood, Alison L. Baird, Sneha Anand, Noel J. Buckley, Abdul Hye, Nicholas J. Ashton, Isabelle Bos, Stephanie J. B. Vos, Mara ten Kate, Philip Scheltens, Charlotte E. Teunissen, Rik Vandenberghe, Silvy Gabel, Karen Meersmans, Sebastiaan Engelborghs, Ellen De Roeck, Kristel Sleegers, Giovanni B. Frisoni, Olivier Blin, Jill Richardson, Régis Bordet, José Luís Molinuevo, Lorena Rami, Anders Wallin, Petronella Kettunen, Magda Tsolaki, Frans R.J. Verhey, Alberto Lleó, Isabel Sala, Julius Popp, Gwendoline Peyratout, Pablo Martínez‐Lage, Mikel Tainta, Peter Johannsen, Yvonne Freund‐Levi, Lutz Frölich, Valerija Dobričić, Cristina Legido‐Quigley, Frederik Barkhof, Ulf Andréasson, Kaj Blennow, Henrik Zetterberg, Johannes Streffer, Christina M. Lill, Lars Bertram, Pieter Jelle Visser, Hartmuth C. Kolb, Vaibhav A. Narayan, Simon Lovestone, Alejo Nevado‐Holgado
Abstract
INTRODUCTION: This study sought to discover and replicate plasma proteomic biomarkers relating to Alzheimer's disease (AD) including both the "ATN" (amyloid/tau/neurodegeneration) diagnostic framework and clinical diagnosis. METHODS: Plasma proteins from 972 subjects (372 controls, 409 mild cognitive impairment [MCI], and 191 AD) were measured using both SOMAscan and targeted assays, including 4001 and 25 proteins, respectively. RESULTS: Protein co-expression network analysis of SOMAscan data revealed the relation between proteins and "N" varied across different neurodegeneration markers, indicating that the ATN variants are not interchangeable. Using hub proteins, age, and apolipoprotein E ε4 genotype discriminated AD from controls with an area under the curve (AUC) of 0.81 and MCI convertors from non-convertors with an AUC of 0.74. Targeted assays replicated the relation of four proteins with the ATN framework and clinical diagnosis. DISCUSSION: Our study suggests that blood proteins can predict the presence of AD pathology as measured in the ATN framework as well as clinical diagnosis.