There is no consensus for a blood-based test for the early diagnosis of Alzheimer’s disease (AD). Expression profiling of small non-coding RNA’s, microRNA (miRNA), has revealed diagnostic potential in human diseases. Circulating miRNA are found in small vesicles known as exosomes within biological fluids such as human serum. The aim of this work was to determine a set of differential exosomal miRNA biomarkers between healthy and AD patients, which may aid in diagnosis. Using next-generation deep sequencing, we profiled exosomal miRNA from serum (N=49) collected from the Australian Imaging, Biomarkers and Lifestyle Flagship Study (AIBL). Sequencing results were validated using quantitative reverse transcription PCR (qRT-PCR; N=60), with predictions performed using the Random Forest method. Additional risk factors collected during the 4.5-year AIBL Study including clinical, medical and cognitive assessments, and amyloid neuroimaging with positron emission tomography were assessed. An AD-specific 16-miRNA signature was selected and adding established risk factors including age, sex and apolipoprotein ɛ4 (APOE ɛ4) allele status to the panel of deregulated miRNA resulted in a sensitivity and specificity of 87% and 77%, respectively, for predicting AD. Furthermore, amyloid neuroimaging information for those healthy control subjects incorrectly classified with AD-suggested progression in these participants towards AD. These data suggest that an exosomal miRNA signature may have potential to be developed as a suitable peripheral screening tool for AD.
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This work was supported by the National Health and Medical Research Council (628946 to AFH and CLM) and project grants from The Judith Jane Mason and Harold Stannett Williams Memorial Foundation and Alzheimer’s Australia (to LC and AFH). LC was supported by a University of Melbourne Early Career Researcher Project Grant for the work and AFH is an Australian Research Council Future Fellow (FT100100560 to AFH). This work was also supported in part by the NHMRC project grant 1071430 to VLV and VLV is supported by an NHMRC Senior Research Fellowship. AIBL was supported by the Science Industry and Endowment Fund (sief.org.au), the McCusker Alzheimer's Research Foundation and the National Health and Medical Research Council via the Dementia Collaborative Research Centres program (DCRC2).
The authors declare no conflict of interest.
Supplementary Information accompanies the paper on the Molecular Psychiatry website
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Cheng, L., Doecke, J., Sharples, R. et al. Prognostic serum miRNA biomarkers associated with Alzheimer’s disease shows concordance with neuropsychological and neuroimaging assessment. Mol Psychiatry 20, 1188–1196 (2015). https://doi.org/10.1038/mp.2014.127
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