Blood Test for Early-Onset Alzheimer's Disease Relies on Exosomal MicroRNA Biomarkers

A team of Australian biomedical researchers has devised a blood test based on expression profiling of small non-coding RNA’s, microRNA (miRNA), for the diagnosis of early-onset Alzheimer's disease (AD).

Investigators at the University of Melbourne (Australia) identified a set of differential exosomal miRNA biomarkers that differentiate between healthy individuals and AD patients. They adapted a panel of these miRNAs—snippets of about 20 nucleotides that block gene expression by attaching to molecules of messenger RNA (mRNA) in a fashion that prevents them from transmitting the protein synthesizing instructions they had received from the DNA—obtained from small serum vesicles known as exosomes for screening of potential AD sufferers.

For this purposed they used a next-generation deep sequencing technique to profile exosomal miRNA from serum collected from 49 participants in the Australian Imaging, Biomarkers, and Lifestyle Flagship Study (AIBL). Sequencing results were validated using quantitative reverse transcription PCR (qRT-PCR). 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 epsilon-4 (APOE epsilon-4) allele status to the miRNA panel resulted in a sensitivity and specificity of 87% and 77%, respectively, for predicting AD.

First author Dr. Lesley Cheng, a post-doctoral researcher in biochemistry, molecular and cell biology at the University of Melbourne, said, “This test provides the possibility of early detection of AD by using a simple blood test which has been designed to also be cost-effective. Furthermore, it is highly accessible for patients and physicians compared to organizing a brain scan or undergoing a neuropsychological test. Patients with a family history of AD or those with memory concerns could be tested during a standard health check at a medical clinic. This test could ease concerns for patients experiencing normal memory problems due to natural ageing. Those identified as high risk could then be monitored by their doctor."

The miRNA biomarker study was published in the October 28, 2014, online edition of the journal Molecular Psychiatry.

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