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

Nicholas Ashton, Steven Kiddle, John Graf, Malcolm Ward, Alison Baird, Abdul Hye, Sarah Westwood, Karyuan Vivian Wong, Richard Dobson, Gil Rabinovici, Bruce Miller, Howard Rosen, Andrew Torres, Zhanpan Zhang, Lennart Thurfjell, Antonia Covin, Christina Hehir, David Baker, Chantal Bazenet, Simon Lovestone

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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.
Original languageEnglish
Pages (from-to)48-60
Number of pages13
JournalAlzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
Volume1
Issue number1
DOIs
Publication statusE-pub ahead of print - 29 Mar 2015

Keywords

  • Plasma
  • β amyloid
  • Proteomics
  • Alzheimer's disease
  • Biomarker
  • Fibrinogen γ-chain
  • Clinical trials

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