Open AccessBlood protein predictors of brain amyloid for enrichment in clinical trials?
Author(s) -
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
Publication year - 2015
Publication title -
alzheimer's and dementia: diagnosis, assessment and disease monitoring
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.497
H-Index - 37
ISSN - 2352-8729
DOI - 10.1016/j.dadm.2014.11.005
Subject(s) - clinical trial , medicine , amyloid β , fibrinogen , cohort , disease , oncology
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.