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

Autor: Ashton NJ; Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; National Institute for Health Research Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley, National Health Service Foundation, London, UK., Kiddle SJ; Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; MRC Social, Genetic and Developmental Psychiatry Centre, King's College London, London, UK., Graf J; GE Global Research, Niskayuna, NY, USA., Ward M; Proteomics Facility, Institute of Psychiatry, Psychology & Neuroscience, Kings College London, London, UK., Baird AL; Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; Department of Psychiatry, University of Oxford, Oxford, UK., Hye A; Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; National Institute for Health Research Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley, National Health Service Foundation, London, UK., Westwood S; Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; National Institute for Health Research Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley, National Health Service Foundation, London, UK., Wong KV; Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK., Dobson RJ; Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; National Institute for Health Research Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley, National Health Service Foundation, London, UK., Rabinovici GD; Memory and Aging Center, University of California, San Francisco, CA, USA., Miller BL; Memory and Aging Center, University of California, San Francisco, CA, USA., Rosen HJ; Memory and Aging Center, University of California, San Francisco, CA, USA., Torres A; GE Global Research, Niskayuna, NY, USA., Zhang Z; GE Global Research, Niskayuna, NY, USA., Thurfjell L; GE Healthcare Life Sciences, Uppsala, Sweden., Covin A; Janssen Research & Development, Neurosciences, Titusville, NJ, USA., Hehir CT; GE Global Research, Niskayuna, NY, USA., Baker D; Janssen Research & Development, Neurosciences, Titusville, NJ, USA., Bazenet C; Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; National Institute for Health Research Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley, National Health Service Foundation, London, UK., Lovestone S; Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; Department of Psychiatry, University of Oxford, Oxford, UK.
Jazyk: angličtina
Zdroj: Alzheimer's & dementia (Amsterdam, Netherlands) [Alzheimers Dement (Amst)] 2015 Mar 29; Vol. 1 (1), pp. 48-60. Date of Electronic Publication: 2015 Mar 29 (Print Publication: 2015).
DOI: 10.1016/j.dadm.2014.11.005
Abstrakt: 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.
Databáze: MEDLINE
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