Evidence map›Paper›PMID 40216989›Full record

ArticleNature aging2025

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

Nimrod Madrer, Shani Vaknine-Treidel, Tamara Zorbaz, Yonat Tzur, Estelle R Bennett, Paz Drori, Nitzan Suissa, David S Greenberg, Eitan Lerner, Eyal Soreq and 2 more

Abstract read
In one paragraph

Article in Nature aging, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Nimrod MadrerEdmond and Lily Safra Center for Brain Sciences, Hebrew University of Jerusalem, Jerusalem, Israel.ORCID http://orcid.org/0000-0002-8467-5085
Shani Vaknine-TreidelEdmond and Lily Safra Center for Brain Sciences, Hebrew University of Jerusalem, Jerusalem, Israel.ORCID http://orcid.org/0000-0003-1424-253X
Tamara ZorbazEdmond and Lily Safra Center for Brain Sciences, Hebrew University of Jerusalem, Jerusalem, Israel.
Yonat TzurEdmond and Lily Safra Center for Brain Sciences, Hebrew University of Jerusalem, Jerusalem, Israel.
Estelle R BennettEdmond and Lily Safra Center for Brain Sciences, Hebrew University of Jerusalem, Jerusalem, Israel.
Paz DroriDepartment of Biological Chemistry, Alexander Silberman Institute of Life Sciences, Faculty of Mathematics and Science, Hebrew University of Jerusalem, Jerusalem, Israel.
Nitzan SuissaDepartment of Neurosurgery, Shaare Zedek Medical Center, Jerusalem, Israel.ORCID http://orcid.org/0009-0001-7646-2952
David S GreenbergEdmond and Lily Safra Center for Brain Sciences, Hebrew University of Jerusalem, Jerusalem, Israel.
Eitan LernerDepartment of Biological Chemistry, Alexander Silberman Institute of Life Sciences, Faculty of Mathematics and Science, Hebrew University of Jerusalem, Jerusalem, Israel.ORCID http://orcid.org/0000-0002-3791-5277
Eyal SoreqUK Dementia Research Institute Care Research and Technology Centre (UK DRI CR&T) at Imperial College London and the University of Surrey, London, UK.
Iddo PaldorDepartment of Biological Chemistry, Alexander Silberman Institute of Life Sciences, Faculty of Mathematics and Science, Hebrew University of Jerusalem, Jerusalem, Israel. iddo.paldor@mail.huji.ac.il.ORCID http://orcid.org/0000-0001-8737-5953
Hermona SoreqEdmond and Lily Safra Center for Brain Sciences, Hebrew University of Jerusalem, Jerusalem, Israel. hermona.soreq@mail.huji.ac.il.ORCID http://orcid.org/0000-0002-0955-526X

Funding

Israel Science Foundation (ISF) 1016/18Israel Science Foundation (ISF) 1770/20Israel Science Foundation (ISF) 3213/19Israel Science Foundation (ISF) 556/22Israel Science Foundation (ISF) 835/23Michael J. Fox Foundation for Parkinson's Research (Michael J. Fox Foundation) 11183
6 · The paper itself

Abstract

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.

Indexed as

Parkinson DiseaseRepetitive Sequences, Nucleic AcidRNA, TransferAgedFemaleHumansMaleMiddle AgedMutationSubstantia NigraRNA, Transfer

Identifiers

PMID40216989
PMCPMC12092246

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.