- 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
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.