title: Blood protein predictors of brain amyloid for enrichment in clinical trials?
abstract: BACKGROUND
  Measures of neocortical amyloid burden (NAB) identify individuals who are at substantially greater risk of developing Alzheimer's disease (AD). Blood-based biomarkers predicting NAB would have great utility for the enrichment of AD clinical trials, including large-scale prevention trials.
  
  
  METHODS
  Nontargeted proteomic discovery was applied to 78 subjects from the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing with a range of NAB values. Technical and independent replications were performed by immunoassay.
  
  
  RESULTS
  Seventeen discovery candidates were selected for technical replication. α2-Macroglobulin, fibrinogen γ-chain (FGG), and complement factor H-related protein 1 were confirmed to be associated with NAB. In an independent cohort, FGG plasma levels combined with age predicted NAB had a sensitivity of 59% and specificity of 78%.
  
  
  CONCLUSIONS
  A single blood protein, FGG, combined with age, was shown to relate to NAB and therefore could have potential for enrichment of clinical trial populations.
authors.affiliation: Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; National Institute for Health Research Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley, National Health Service Foundation, London, UK.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Ashton
authors.affiliation: Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; MRC Social, Genetic and Developmental Psychiatry Centre, King's College London, London, UK.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Kiddle
authors.affiliation: GE Global Research, Niskayuna, NY, USA.
authors.forename: John
authors.initials: J
authors.lastname: Graf
authors.affiliation: Proteomics Facility, Institute of Psychiatry, Psychology & Neuroscience, Kings College London, London, UK.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Ward
authors.affiliation: Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; Department of Psychiatry, University of Oxford, Oxford, UK.
authors.forename: Alison L
authors.initials: AL
authors.lastname: Baird
authors.affiliation: Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; National Institute for Health Research Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley, National Health Service Foundation, London, UK.
authors.forename: Abdul
authors.initials: A
authors.lastname: Hye
authors.affiliation: Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; National Institute for Health Research Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley, National Health Service Foundation, London, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Westwood
authors.affiliation: Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
authors.forename: Karyuan Vivian
authors.initials: KV
authors.lastname: Wong
authors.affiliation: Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; National Institute for Health Research Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley, National Health Service Foundation, London, UK.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Dobson
authors.affiliation: Memory and Aging Center, University of California, San Francisco, CA, USA.
authors.forename: Gil D
authors.initials: GD
authors.lastname: Rabinovici
authors.affiliation: Memory and Aging Center, University of California, San Francisco, CA, USA.
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Miller
authors.affiliation: Memory and Aging Center, University of California, San Francisco, CA, USA.
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Rosen
authors.affiliation: GE Global Research, Niskayuna, NY, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Torres
authors.affiliation: GE Global Research, Niskayuna, NY, USA.
authors.forename: Zhanpan
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: GE Healthcare Life Sciences, Uppsala, Sweden.
authors.forename: Lennart
authors.initials: L
authors.lastname: Thurfjell
authors.affiliation: Janssen Research & Development, Neurosciences, Titusville, NJ, USA.
authors.forename: Antonia
authors.initials: A
authors.lastname: Covin
authors.affiliation: GE Global Research, Niskayuna, NY, USA.
authors.forename: Cristina Tan
authors.initials: CT
authors.lastname: Hehir
authors.affiliation: Janssen Research & Development, Neurosciences, Titusville, NJ, USA.
authors.forename: David
authors.initials: D
authors.lastname: Baker
authors.affiliation: Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; National Institute for Health Research Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley, National Health Service Foundation, London, UK.
authors.forename: Chantal
authors.initials: C
authors.lastname: Bazenet
authors.affiliation: Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; Department of Psychiatry, University of Oxford, Oxford, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Lovestone
keywords: Alzheimer's disease; Biomarker; Clinical trials; Fibrinogen γ-chain; Plasma; Proteomics; β amyloid