Researchers have developed a simple and cost-effective blood test capable of detecting Parkinson’s disease long before symptoms emerge, comparing the current state of diagnosing neurodegenerative diseases to the fight against cancer 50 years ago—when most cases were identified too late for effective treatment. The test quantifies specific RNA fragments in the blood, focusing on a repetitive RNA sequence that accumulates in Parkinson’s patients and a parallel decline in mitochondrial RNA, which deteriorates as the disease progresses. By measuring the ratio between these biomarkers, the test offers a highly accurate, non-invasive, rapid  and affordable diagnostic tool, providing hope for early interventions and treatments that could change the course of the disease.

Diagnosis of neurodegenerative diseases is these days at the level that cancer diagnosis was 50 years ago: disease is identified when most of the relevant neurons have already died, and it is therefore too late to cure. To address this problem, researchers at the Hebrew University of Jerusalem have unveiled a groundbreaking blood test that could revolutionize an early diagnosis of Parkinson’s disease (PD), paving the way for timely interventions and improved patient outcomes. The study, published in Aging Nature, led by PhD student Nimrod Madrer under the supervision of Prof. Hermona Soreq at The Edmond and Lily Safra Center for Brain Sciences (ELSC) and The Alexander Silberman Institute of Life Sciences, at the Hebrew University, in collaboration with Dr. Iddo Paldor from the Shaare Zedek Medical Center, and Dr. Eyal Soreq from University of Surrey and the Imperial College London. Intriguingly, it introduces a novel approach to detecting PD at its earliest stages through the analysis of transfer RNA fragments (tRFs).

Traditionally overlooked in Parkinson’s research, tRFs (transfer RNA fragments) are small RNA molecules with the potential to reveal significant changes in the body linked to neurodegeneration. The researchers identified two key biomarkers—an increase in PD-specific tRFs carrying a conserved sequence motif (RGTTCRA-tRFs) and a decrease in mitochondrial tRFs (MT-tRFs). By measuring the ratio between these biomarkers, the new test can distinguish pre-symptomatic Parkinson’s patients from healthy controls with an accuracy surpassing that of existing clinical diagnostic tools.

“This discovery represents a major advancement in our understanding of Parkinson’s disease and offers a simple, minimally-invasive blood test as a tool for early diagnosis,” said Prof. Hermona Soreq. “By focusing on tRFs, we’ve opened a new window into the molecular changes that occur in the earliest stages of the disease.”

Technical representation of the datasets and methods

a. The different datasets used in this work with total number of samples in each. All datasets were subjected to files quality check (using FASTQC), adaptor removal (FLEXBAR) and alignment to tRFs (MINTmap). b. DE analysis using EdgeR was applied on CSF (PD vs. Ctrl) and SN (high vs. low Lewy body score) samples. c. The consensus motif sequence identified by the MEME tool. Letters heights: Nucleotides conservation among upregulated N-tRFs. d. PPMI samples were further divided to subgroups according to the relevant comparison, with prodromal PD patients (n = 189) divided to 60 + 60 optimally matched patients and controls, 33 + 33 optimally matched test data, and 60 + 110 fully matched patients and controls. e, f. Calculated sum (E) and percentage (F) for RGTTCRA-tRFs and MT-tRFs (and their ratio – RGTTCRA-tRFs/MT-tRFs) from all blood samples. g. Normalized calculated PD/MT-tRFs ratio for the two prodromal groups. h. The optimally matched patients served as a training dataset (GBM, k = 5 folds). i. Naïve test data and Fully matched patients served as a testing dataset. j. Blood samples collected in Jerusalem and SN samples obtained from the NIH NeuroBioBank served to test qPCR segregation of PD from controls using the primers designed based on the PPMI prodromal data. k. Long-RNA Affymetrix data (GSE23676) served to map Angiogenin levels in 7 PD patients before and after DBS neurosurgery.

The test employs a straightforward, dual qPCR assay, measuring the ratio between the repeated short motif and an exemplary mitochondrial sequence, making it cost-effective and accessible for use in a wide range of healthcare settings. In trials involving samples from multiple international cohorts, including the Parkinson’s Progression Markers Initiative, the test achieved a diagnostic accuracy of 0.86, significantly outperforming traditional clinical scoring methods. Moreover, the study found that RGTTCRA-tRF levels decrease following deep brain stimulation, further linking these RNA fragments to both disease mechanisms and treatment responses.

Lead researcher Nimrod Madrer emphasized the importance of early detection, noting that Parkinson’s disease is often diagnosed only after significant brain damage has occurred. “This test has the potential to alleviate the uncertainty faced by patients and clinicians, offering a reliable and rapid method to identify the disease in its earliest stages,” Madrer stated.

The findings have been published under US Provisional Patent Applications, and large scale diagnostic tests provided broader clinical validation. This research represents a significant milestone in the fight against Parkinson’s disease, offering new hope for millions of people worldwide.

Source – The Hebrew University of Jerusalem