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Replication study of plasma proteins relating to Alzheimer's pathology
Author(s) -
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,
MartinezLage Pablo,
Tainta Mikel,
Johannsen Peter,
FreundLevi Yvonne,
Frölich Lutz,
Dobricic Valerija,
LegidoQuigley 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,
NevadoHolgado Alejo J.
Publication year - 2021
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.12322
Subject(s) - neurodegeneration , blood proteins , apolipoprotein e , proteomics , biomarker , alzheimer's disease , pathology , medicine , disease , biology , bioinformatics , gene , genetics
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.