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; Group, AIBL Research

doi:10.1016/j.dadm.2014.11.005

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

Published Web Location

https://doi.org/10.1016/j.dadm.2014.11.005

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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