@article{3ce2813b2b8b46449544f7dae56f54ae,
title = "Detecting amyloid positivity in early Alzheimer's disease using combinations of plasma Aβ42/Aβ40 and p-tau",
abstract = "Introduction: We studied usefulness of combining blood amyloid beta (Aβ)42/Aβ40, phosphorylated tau (p-tau)217, and neurofilament light (NfL) to detect abnormal brain Aβ deposition in different stages of early Alzheimer's disease (AD). Methods: Plasma biomarkers were measured using mass spectrometry (Aβ42/Aβ40) and immunoassays (p-tau217 and NfL) in cognitively unimpaired individuals (CU, N = 591) and patients with mild cognitive impairment (MCI, N = 304) from two independent cohorts (BioFINDER-1, BioFINDER-2). Results: In CU, a combination of plasma Aβ42/Aβ40 and p-tau217 detected abnormal brain Aβ status with area under the curve (AUC) of 0.83 to 0.86. In MCI, the models including p-tau217 alone or Aβ42/Aβ40 and p-tau217 had similar AUCs (0.86–0.88); however, the latter showed improved model fit. The models were implemented in an online application providing individualized risk assessments (https://brainapps.shinyapps.io/PredictABplasma/). Discussion: A combination of plasma Aβ42/Aβ40 and p-tau217 discriminated Aβ status with relatively high accuracy, whereas p-tau217 showed strongest associations with Aβ pathology in MCI but not in CU.",
keywords = "Alzheimer's disease, Aβ42/Aβ40, amyloid, blood biomarkers, neurofilament light, p-tau217",
author = "Shorena Janelidze and Sebastian Palmqvist and Antoine Leuzy and Erik Stomrud and Verberk, {Inge M. W.} and Henrik Zetterberg and Ashton, {Nicholas J.} and Pedro Pesini and Leticia Sarasa and Allu{\'e}, {Jos{\'e} Antonio} and Teunissen, {Charlotte E.} and Dage, {Jeffrey L.} and Kaj Blennow and Niklas Mattsson-Carlgren and Oskar Hansson",
note = "Funding Information: The study was supported by the Swedish Research Council (2016‐00906); the Knut and Alice Wallenberg Foundation (2017‐0383); the Marianne and Marcus Wallenberg Foundation (2015.0125); the Strategic Research Area MultiPark (Multidisciplinary Research in Parkinson's disease) at Lund University, the Swedish Alzheimer Foundation (AF‐745911, AF‐846521); the Swedish Brain Foundation (FO2019‐0326); The Parkinson Foundation of Sweden (1280/20); the Sk{\aa}ne University Hospital Foundation (2020‐O000028); Regionalt Forskningsst{\"o}d (2020‐0314); The Bundy Academy; the Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse; and the Swedish federal government under the ALF agreement (2018‐Projekt0279), the European Commission (Marie Curie International Training Network, JPND), Health Holland, the Dutch Research Council (ZonMW), Alzheimer Drug Discovery Foundation, The Selfridges Group Foundation, Alzheimer Netherlands, Alzheimer Association. The funding sources had no role in the design and conduct of the study; in the collection, analysis, interpretation of the data; or in the preparation, review, or approval of the manuscript. The precursor of [F]flutemetamol was provided by GE Healthcare. Analysis of plasma p‐tau217 and Aβ42/Aβ40 were performed at Eli Lilly and Company and Araclon Biotech Ltd, respectively. Analysis of CSF Aβ42/Aβ40 was performed at Euroimmun. 18 Publisher Copyright: {\textcopyright} 2021 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
doi = "10.1002/alz.12395",
language = "English",
journal = "Alzheimers & Dementia",
issn = "1552-5260",
publisher = "Elsevier",
}