Replication study of plasma proteins relating to Alzheimer's pathology

Liu Shi*, Laura M. Winchester, Sarah Westwood, Alison L. Baird, Sneha N. 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 E. de Roeck, Kristel Sleegers, Giovanni B. FrisoniOlivier Blin, Jill C. Richardson, R. gis Bordet, José L. Molinuevo, Lorena Rami, Anders Wallin, Petronella Kettunen, Magda Tsolaki, Frans Verhey, Alberto Lléo, Isabel Sala, Julius Popp, Gwendoline Peyratout, Pablo Martinez-Lage, Mikel Tainta, Peter Johannsen, Yvonne Freund-Levi, Lutz Frölich, Valerija Dobricic, Cristina Legido-Quigley, Frederik Barkhof, Ulf Andreasson, Kaj Blennow, Henrik Zetterberg, Johannes Streffer, Christina M. Lill, Lars Bertram, Pieter Jelle Visser, Hartmuth C. Kolb, Vaibhav A. Narayan, Simon Lovestone, Alejo J. Nevado-Holgado

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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.
Original languageEnglish
JournalAlzheimer's and Dementia
Early online date2021
DOIs
Publication statusE-pub ahead of print - 2021

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