The diagnosis of Parkinson's is usually not established until advanced neurodegeneration leads to clinically detectable symptoms involving the malfunction and death of vital nerve cells in the brain.

Previous studies of Parkinson’s disease transcriptome show low concordance, possibly resulting from the use of microarray technology, which has high measurement variation, but a new blood test may more accurately identify blood signatures, or biomarkers, for Parkinson’s disease (PD).

Scientists at the Icahn School of Medicine at Mount Sinai (New York, NY, USA) and their colleagues analyzed the blood of four groups of mice with genetic material (ribonucleic acids or RNA) predicted by the investigators to form part of a PD signature. They also examined the blood of a group of 34 Ashkenazi Jewish patients living with PD, as well as a separate group of healthy controls. The male to female ratio was higher in the PD group who were slightly older.

Total RNA was extracted from human venous blood using the PAXgene blood miRNA kit (Qiagen, Venlo, The Netherlands). Using 100 ng of total RNA, messenger RNA (mRNA) levels were assayed by direct digital detection (NanoString Technologies; Seattle, WA, USA). The 113-marker human panel was developed based on the mouse results as well as markers selected from other published PD blood biomarker studies.

About half of the human subjects, both symptomatic PD patients and healthy controls, have small changes in their DNA code called mutations, in a gene known to increase the likelihood of developing Parkinson’s: leucine-rich repeat kinase 2, or LRRK2. Just 1% to 2% of Parkinson’s patients carry this gene mutation, and many LRRK2 mutation carriers are from the Ashkenazi Jewish population. The other samples studied came from individuals without the mutation, half of whom had clinical PD. After comparing the mouse and human blood samples, the team identified RNA signatures that can be measured in blood samples that correlate with the disease-causing mutations in the LRRK2 gene in PD patients.

Stuart Sealfon, MD, chairman and Glickenhaus professor of neurology, and senior author of the study said, “The goal of this study was to improve early disease detection, especially in people who are carrying a predisposing genetic mutation. If you can improve your ability to diagnose the disease more specifically and identify new subtypes, this can help overcome the hurdle in developing new treatments for Parkinson’s and other brain diseases. The next step is to replicate this approach in a larger sample, where we track patients longitudinally and see how profiles are changing over time.” The study was first published online on March 18, 2015, in the journal Movement Disorders.

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Icahn School of Medicine at Mount Sinai 
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