Prognostic serum miRNA biomarkers associated with Alzheimer’s disease shows concordance with neuropsychological and neuroimaging assessment
Abstract
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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A distinctive AD-specific signature comprised of 16 miRNAs demonstrated high predictive accuracy, with a sensitivity of 87% and specificity of 77% for AD diagnosis.
“Utilizing unbiased next-generation deep sequencing followed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) for validation, they identified a distinctive AD-specific signature comprised of 16 miRNAs. This signature demonstrated high predictive accuracy, with a sensitivity of 87% and specificity of 77% for AD diagnosis.”
From Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions (2024) · cites this paper as [154]
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- Authors
- Cheng, L., Doecke, J. D., Sharples, R. A., Villemagne, V. L., Fowler, C. J., Rembach, A., Martins, R. N., Rowe, C. C., Macaulay, S. L., Masters, C. L., Hill, A. F., & for the Australian Imaging, B. A. L. (. R. G.
- Affiliations
- The University of Melbourne (AU)
- Commonwealth Scientific and Industrial Research Organisation (AU)
- Florey Institute of Neuroscience and Mental Health (AU)
- Edith Cowan University (AU)
- Austin Hospital (AU)
- Corresponding author
- Hill, A F
- ORCID
- Venue
- Molecular Psychiatry
- Published
- 2014-10-28
- Volume
- 20
- Issue
- 10
- Pages
- 1188-1196
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- OpenAlex
- W2006986124
- Cited by
- 409
- References
- 6
- Citations by year
- 2026: 13 · 2025: 29 · 2024: 37 · 2023: 35 · 2022: 54 · 2021: 51 · 2020: 43 · 2019: 48 · 2018: 28 · 2017: 27 · 2016: 24 · 2015: 18
- FWCI
- 17.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Victoria University Research Repository (Victoria University) (submittedVersion)
- Research Online (Edith Cowan University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Keywords
- Alzheimer's disease, exosomal microRNAs, serum biomarkers, blood-based diagnosis, early diagnosis, microRNA signature, APOE ε4, amyloid PET, peripheral biomarkers, sensitivity and specificity
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Female, Genetic Testing, Humans, Male, Neuropsychological Tests, Prognosis, Sensitivity and Specificity, Reproducibility of Results, Biomarkers, Case-Control Studies, Sequence Analysis, RNA, MicroRNAs, Exosomes, Transcriptome, Neuroimaging
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