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

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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.

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APA

Ashton, N. J., Kiddle, S. J., Graf, J., Ward, M., Baird, A. L., Hye, A., … Lovestone, S. (2015). Blood protein predictors of brain amyloid for enrichment in clinical trials? Alzheimer’s and Dementia: Diagnosis, Assessment and Disease Monitoring, 1(1), 48–60. https://doi.org/10.1016/j.dadm.2014.11.005

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