Journal article
A plasma protein classifier for predicting amyloid burden for preclinical Alzheimer’s disease
NJ Ashton, AJ Nevado-Holgado, IS Barber, S Lynham, V Gupta, P Chatterjee, K Goozee, E Hone, S Pedrini, K Blennow, M Schöll, H Zetterberg, KA Ellis, AI Bush, CC Rowe, VL Villemagne, D Ames, CL Masters, D Aarsland, J Powell Show all
Science Advances | AMER ASSOC ADVANCEMENT SCIENCE | Published : 2019
Abstract
A blood-based assessment of preclinical disease would have huge potential in the enrichment of participants for Alzheimer’s disease (AD) therapeutic trials. In this study, cognitively unimpaired individuals from the AIBL and KARVIAH cohorts were defined as A negative or A positive by positron emission tomography. Nontargeted proteomic analysis that incorporated peptide fractionation and high-resolution mass spectrometry quantified relative protein abundances in plasma samples from all participants. A protein classifier model was trained to predict A-positive participants using feature selection and machine learning in AIBL and independently assessed in KARVIAH. A 12-feature model for predict..
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Awarded by Medical Research Council
Funding Acknowledgements
We express our appreciation to all participants in the AIBL and KARVIAH studies. This paper presents independent research funded by Butterfield Trust via Rosetree Trust UK. N.J.A. was supported by Rosetree Trust for this study. P.C. is supported by KaRa Institute of Neurological Diseases (KaRa MINDS) and Macquarie University. K.G. is funded by Anglicare (Sydney, Australia). H.Z. is a Wallenberg Academy Fellow and acknowledges support from the UK Dementia Research Institute. A.I.B. is funded by the National Health and Medical Research Council (GNT1103703, GNT1132604, and GNT1103703) and the Cooperative Research Centre for Mental Health. S. Lovestone is funded by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre and named in inventor on biomarker intellectual property protected by Proteome Science and King's College London (unrelated to this study). R.M. is funded jointly by Edith Cowan University and Macquarie University. A.H. is funded by the Research Centre for Mental Health and Biomedical Research Unit for dementia. All other authors acknowledge that they received no funding in support of this research. This study represents independent research part funded by the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care.