#743

Pre-symptomatic Parkinson’s disease blood test quantifying repetitive sequence motifs in transfer RNA fragments 2025

Early, efficient Parkinson’s disease (PD) tests may facilitate pre-symptomatic diagnosis and disease-modifying therapies. Here we report elevated levels of PD-specific transfer RNA fragments carrying a conserved sequence motif (RGTTCRA-tRFs) in the substantia nigra, cerebrospinal fluid and blood of patients with PD. A whole blood qPCR test detecting elevated RGTTCRA-tRFs and reduced mitochondrial-originated tRFs (MT-tRFs) segregated pre-symptomatic patients with PD from controls (area under the receiver operating characteristic curve (ROC-AUC) of 0.75 versus 0.71 based on traditional clinical scoring). Strengthening PD relevance, patients carrying PD-related mutations presented higher blood RGTTCRA-tRFs/MT-tRFs ratios than mutation-carrying non-symptomatic controls, and RGTTCRA-tRF levels decreased in patients’ blood after deep brain stimulation. Furthermore, RGTTCRA-tRFs complementarity to ribosomal RNA and the translation-supporting LeuCAG3-tRF might aggravate PD via translational inhibition, as reflected by disrupted ribosomal association of RGTTCRA-tRFs in depolarized neuroblastoma cells. Our findings show tRF involvement in PD and suggest a potential simple and safe blood test that may aid clinicians in pre-symptomatic PD diagnosis after validation in larger independent cohorts.

Transfer RNA fragments (tRFs) are 16–50 nucleotide (nt)-long, non-coding RNAs originating from multiple nuclear or mitochondrial transfer RNA (tRNA) genes. Several enzymes cleave tRNAs to yield tRFs: angiogenin (Ang) generates 5′-half and 3′-half tRFs, whereas Ang, Dicer and other nucleases yield 5′-tRFs, i-tRFs and 3′-tRFs26. Because tRFs harbor repetitive sequence motifs inherited from their parental tRNAs, changes can be detected in an entire family of closely related transcripts, albeit of different origins and types, produced by different endonucleases, and originating from either nuclear or mitochondrial genomes. Correspondingly, tRFs may reflect transcriptional changes or malfunctions in both the nucleus and the mitochondria, whose DNA is known to be damaged in PD. Intriguingly, altered Ang levels, Ang mutations and Ang-produced tRFs may exert both PD-protective and cytotoxic roles. Furthermore, blood cell tRF levels present diagnostic value in various diseases, including ischemic stroke, amyotrophic lateral sclerosis, epilepsy and cellular or organismal stress. Accordingly, tRFs emerge as the perfect candidates for a blood-based PD biomarker.

Press: RNA-based blood test identifies Parkinson’s before symptoms appear

@John_Hemming

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#744

What people miss is when the mtDNA is damaged this results in splicing and other transcriptional changes. That causes the phenotype of aging/parkinsons. The reason this is more obvious in parkinsons in the substantia nigra is because of its proximity to the third ventricle.

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#745

I had not heard of this before:

Age and genetic predisposition play a role. But Bloem and the wider neurological community contend that those two factors alone cannot explain the steep rise in cases. In a 2024 paper co-authored with U.S. neurologist Ray Dorsey, Bloem wrote that Parkinson’s is “predominantly an environmental disease” — a condition shaped less by genetics and more by prolonged exposure to toxicants like air pollution, industrial solvents and, above all, pesticides.

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#746

And some good news:

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#747

Most know that paraquat is a dangerous chemical. I’ve been told several times. We don’t use it, though I’ve seen it and can get it. Most herbicide is pretty safe. Roundup has a lot of talk about causing cancer and there have been court cases won which is now breaking Bayer. Some may celebrate, but the chemicals needed to replace it will be worse. Roundup is tightly bound to the surface of the soil and broken down. It never enters the ground water. A good feature.

#748

Just read about this new medication - treatment.
The once-daily pill, tavapadon.

Link: New Parkinson's medication alleviates symptoms without common side effects | Fox News