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

Research output: Contribution to journalArticlepeer-review

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

Original languageEnglish
Pages (from-to)48-60
Number of pages13
JournalAlzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
Issue number1
E-pub ahead of print29 Mar 2015


  • pre_print

    pre_print.pdf, 363 KB, application/pdf

    Uploaded date:24 Feb 2016

    Version:Accepted author manuscript

  • 1_s2.0_S2352872915000081_main

    1_s2.0_S2352872915000081_main.pdf, 4.91 MB, application/pdf

    Uploaded date:25 Feb 2016

    Version:Final published version

    Licence:CC BY-NC-ND

King's Authors


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.

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.

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%.

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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