Replication study of plasma proteins relating to Alzheimer's pathology.
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Shi Liu, Winchester Laura M, Westwood Sarah, Baird Alison L, Anand Sneha N, Buckley Noel J, Hye Abdul, Ashton Nicholas J, Bos Isabelle, Vos Stephanie J B, Kate Mara Ten, Scheltens Philip, Teunissen Charlotte E, Vandenberghe Rik, Gabel Silvy, Meersmans Karen, Engelborghs Sebastiaan, De Roeck Ellen E, Sleegers Kristel, Frisoni Giovanni B, Blin Olivier, Richardson Jill C, Bordet Régis, Molinuevo José L, Rami Lorena, Wallin Anders, Kettunen Petronella, Tsolaki Magda, Verhey Frans, Lléo Alberto, Sala Isabel, Popp Julius, Peyratout Gwendoline, Martinez-Lage Pablo, Tainta Mikel, Johannsen Peter, Freund-Levi Yvonne, Frölich Lutz, Dobricic Valerija, Legido-Quigley Cristina, Barkhof Frederik, Andreasson Ulf, Blennow Kaj, Zetterberg Henrik, Streffer Johannes, Lill Christina M, Bertram Lars, Visser Pieter Jelle, Kolb Hartmuth C, Narayan Vaibhav A, Lovestone Simon, Nevado-Holgado Alejo J
Аннотация
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.