Blood test may detect Parkinson’s in earliest stages: Study
Changes in transfer RNA fragments evident before symptoms appear
Scientists have developed a blood test to detect Parkinson’s disease in its very early stages, before a person experiences the first symptoms that would normally prompt a Parkinson’s diagnosis, a study showed.
After identifying that people with Parkinson’s have alterations in two types of transfer RNA fragments (tRFs), molecules that play a variety of roles in cellular function, researchers developed a diagnostic test to measure the ratio between the molecules. The test was able to accurately distinguish between people with presymptomatic Parkinson’s and those without it.
Advantages of the test, according to the authors, is that it is minimally invasive, quick, and cost effective.
“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,” Nimrod Madrer, the study’s first author and a PhD student at the Hebrew University of Jerusalem, said in a university news story.
The study, “Pre-symptomatic Parkinson’s disease blood test quantifying repetitive sequence motifs in transfer RNA fragments,” was published in Nature Aging.
Test for Parkinson’s
Parkinson’s disease is characterized by the progressive loss of nerve cells that produce a brain-signaling chemical called dopamine.
It is generally diagnosed when a person shows motor symptoms characteristic of the disease, but this doesn’t usually occur until most affected cells have already died off. That points to a need for diagnostic tests that can identify the disease in its earlier stages so that appropriate Parkinson’s treatment can be started sooner.
“Ideally, an easy, safe and affordable diagnosis should be based on multiple highly sensitive and specific blood biomarkers,” the researchers wrote.
The blood test described in the study is designed to detect Parkinson’s in very early stages by measuring levels of certain tRFs in the blood.
It’s thought that alterations in tRFs may reflect disease-related changes, and as such, they could have value as diagnostic biomarkers for conditions such as Parkinson’s.
The scientists performed a series of experiments to identify a Parkinson’s-specific tRF profile. They looked at RNA sequencing data from people with and without the disease. RNA sequencing looks at the string of nucleotides (DNA and RNA building blocks) that make up RNA to identify any possible changes.
Ultimately, the scientists identified two apparent tRF changes that could be observed in Parkinson’s but which were not seen in healthy people or people with Alzheimer’s disease.
They found that tRFs that originated in the cell’s nucleus — its DNA-containing core — were elevated at various stages of Parkinson’s, with observable changes in the cerebrospinal fluid (the fluid surrounding the brain and spinal cord), brain tissue, and blood. The tRFs that were elevated were found to have a particular motif, or string of nucleotides, called RGTTCRA embedded in their sequence.
In other experiments, RGTTCRA-tRFs appeared to be closely linked to disease progression. Deep brain stimulation, a therapeutic approach for advanced Parkinson’s, was associated with reductions in RGTTCRA tRF blood levels.
On the other hand, tRFs originating from the mitochondria were reduced in the CSF and brain tissue of people with Parkinson’s, and in the blood of certain early Parkinson’s patients. Mitochondria are the cellular compartments responsible for energy production, and are known to be damaged in Parkinson’s.
Based on these observations, the scientists developed a biomarker assay that would measure the ratio between RGTTCRA-tRFs and mitochondrial tRFs in a blood sample. They performed a series of validation experiments to confirm its diagnostic utility.
They found the test could distinguish between healthy people and people who showed very early signs of Parkinson’s but who did not have a formal diagnosis, known as the presymptomatic or prodromal stage. The biomarker test was able to outperform standard diagnostic clinical tests.
Patients with Parkinson’s-related gene mutations also had higher blood RGTTCRA-tRFs/MT-tRFs ratios than people with the same mutations who didn’t show any symptoms.
“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 Hermona Soreq, PhD, the study’s senior author and a professor of molecular neuroscience at Hebrew University. “By focusing on tRFs, we’ve opened a new window into the molecular changes that occur in the earliest stages of the disease.”
Although the findings are promising, the scientists said there’s a need for long-term studies to follow patients as their disease progresses in order to understand how these biomarkers change over time and with treatment, and to validate the test’s utility in a more diverse group of people.
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