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Blood protein predictors of brain amyloid for enrichment in clinical trials?

  • Author(s): Ashton, Nicholas J
  • Kiddle, Steven J
  • Graf, John
  • Ward, Malcolm
  • Baird, Alison L
  • Hye, Abdul
  • Westwood, Sarah
  • Wong, Karyuan Vivian
  • Dobson, Richard J
  • Rabinovici, Gil D
  • Miller, Bruce L
  • Rosen, Howard J
  • Torres, Andrew
  • Zhang, Zhanpan
  • Thurfjell, Lennart
  • Covin, Antonia
  • Hehir, Cristina Tan
  • Baker, David
  • Bazenet, Chantal
  • Lovestone, Simon
  • AIBL Research Group
  • et al.
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%. CONCLUSION: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.

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